diff --git a/CHANGELOG.md b/CHANGELOG.md
index 6b0ac581b..295c55db9 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -5,6 +5,9 @@
 ### Fixed
 - Fixed copying of `TypeMap` and `TypeConfigurator`. Previously, the same global `TypeConfigurator` instance was used in all copies of a `TypeMap`. @rly [#1302](https://github.com/hdmf-dev/hdmf/pull/1302)
 - Fixed `get_data_shape` to use `Data.data.shape` instead of `Data.shape`, which may be overridden by subclasses. @rly [#1311](https://github.com/hdmf-dev/hdmf/pull/1311)
+- Added a check when setting or adding data to a `DynamicTableRegion` or setting the `table` attribute of a `DynamicTableRegion`
+  that the data values are in bounds of the linked table. This can be turned off for
+  `DynamicTableRegion.__init__` using the keyword argument `validate_data=False`. @rly [#1168](https://github.com/hdmf-dev/hdmf/pull/1168)
 
 ### Added
 - Added a check for a compound datatype that is not defined in the schema or spec. This is currently not supported. @mavaylon1 [#1276](https://github.com/hdmf-dev/hdmf/pull/1276)
diff --git a/src/hdmf/common/table.py b/src/hdmf/common/table.py
index f4b2cd011..62ab7f535 100644
--- a/src/hdmf/common/table.py
+++ b/src/hdmf/common/table.py
@@ -1404,17 +1404,45 @@ class DynamicTableRegion(VectorData):
         'table',
     )
 
+    MAX_ROWS_TO_VALIDATE_INIT = int(1e3)
+
     @docval({'name': 'name', 'type': str, 'doc': 'the name of this VectorData'},
             {'name': 'data', 'type': ('array_data', 'data'),
              'doc': 'a dataset where the first dimension is a concatenation of multiple vectors'},
             {'name': 'description', 'type': str, 'doc': 'a description of what this region represents'},
             {'name': 'table', 'type': DynamicTable,
              'doc': 'the DynamicTable this region applies to', 'default': None},
+            {'name': 'validate_data', 'type': bool,
+             'doc': 'whether to validate the data is in bounds of the linked table', 'default': True},
             allow_positional=AllowPositional.WARNING)
     def __init__(self, **kwargs):
-        t = popargs('table', kwargs)
+        table, validate_data = popargs('table', 'validate_data', kwargs)
+        data = getargs('data', kwargs)
+        self._validate_data = validate_data
+        if self._validate_data:
+            self._validate_index_in_range(data, table)
+
         super().__init__(**kwargs)
-        self.table = t
+        if table is not None:  # set the table attribute using fields to avoid another validation in the setter
+            self.fields['table'] = table
+
+    def _validate_index_in_range(self, data, table):
+        """If the length of data is small, and if data contains an index that is out of bounds, then raise an error.
+        If the object is being constructed from a file, raise a warning instead to ensure invalid data can still be
+        read.
+        """
+        if table and len(data) <= self.MAX_ROWS_TO_VALIDATE_INIT:
+            if isinstance(data, (list, tuple)):
+                data_arr = np.array(data)
+            else:
+                data_arr = data[:]
+            violators = np.where((data_arr >= len(table)) | (data_arr < 0))[0]
+            if violators.size > 0:
+                error_msg = (
+                    f"DynamicTableRegion values {data_arr[violators]} are out of bounds for "
+                    f"{type(table)} '{table.name}'."
+                )
+                self._error_on_new_warn_on_construct(error_msg, error_cls=IndexError)
 
     @property
     def table(self):
@@ -1422,24 +1450,27 @@ def table(self):
         return self.fields.get('table')
 
     @table.setter
-    def table(self, val):
+    def table(self, table):
         """
-        Set the table this DynamicTableRegion should be pointing to
+        Set the table this DynamicTableRegion should be pointing to.
+
+        If the length of the data is small, this will validate all data elements in this DynamicTableRegion to
+        ensure they are within bounds.
 
-        :param val: The DynamicTable this DynamicTableRegion should be pointing to
+        :param table: The DynamicTable this DynamicTableRegion should be pointing to
 
         :raises: AttributeError if table is already in fields
         :raises: IndexError if the current indices are out of bounds for the new table given by val
         """
-        if val is None:
+        if table is None:
             return
         if 'table' in self.fields:
             msg = "can't set attribute 'table' -- already set"
             raise AttributeError(msg)
-        dat = self.data
-        if isinstance(dat, DataIO):
-            dat = dat.data
-        self.fields['table'] = val
+
+        self.fields['table'] = table
+        if self._validate_data:
+            self._validate_index_in_range(self.data, table)
 
     def __getitem__(self, arg):
         return self.get(arg)
@@ -1583,6 +1614,12 @@ def _validate_on_set_parent(self):
             warn(msg, stacklevel=2)
         return super()._validate_on_set_parent()
 
+    def _validate_new_data_element(self, arg):
+        """Validate that the new index is within bounds of the table. Raises an IndexError if not."""
+        if self.table and (arg >= len(self.table) or arg < 0):
+            raise IndexError(f"DynamicTableRegion index {arg} is out of bounds for "
+                             f"{type(self.table)} '{self.table.name}'.")
+
 
 def _uint_precision(elements):
     """ Calculate the uint precision needed to encode a set of elements """
diff --git a/src/hdmf/container.py b/src/hdmf/container.py
index dd30d208b..33100e9a5 100644
--- a/src/hdmf/container.py
+++ b/src/hdmf/container.py
@@ -573,6 +573,19 @@ def _validate_on_set_parent(self):
         """
         pass
 
+    def _error_on_new_warn_on_construct(self, error_msg: str, error_cls: type = ValueError):
+        """Raise a ValueError when a check is violated on instance creation.
+        To ensure backwards compatibility, this method throws a warning
+        instead of raising an error when reading from a file, ensuring that
+        files with invalid data can be read. If error_msg is set to None
+        the function will simply return without further action.
+        """
+        if error_msg is None:
+            return
+        if not self._in_construct_mode:
+            raise error_cls(error_msg)
+        warn(error_msg)
+
 
 class Container(AbstractContainer):
     """A container that can contain other containers and has special functionality for printing."""
diff --git a/tests/unit/build_tests/test_classgenerator.py b/tests/unit/build_tests/test_classgenerator.py
index 16136a8da..6199c679d 100644
--- a/tests/unit/build_tests/test_classgenerator.py
+++ b/tests/unit/build_tests/test_classgenerator.py
@@ -1,5 +1,4 @@
 import numpy as np
-import os
 import shutil
 import tempfile
 from warnings import warn
@@ -659,9 +658,6 @@ class TestGetClassSeparateNamespace(TestCase):
 
     def setUp(self):
         self.test_dir = tempfile.mkdtemp()
-        if os.path.exists(self.test_dir):  # start clean
-            self.tearDown()
-        os.mkdir(self.test_dir)
 
         self.bar_spec = GroupSpec(
             doc='A test group specification with a data type',
@@ -843,9 +839,6 @@ class TestGetClassObjectReferences(TestCase):
 
     def setUp(self):
         self.test_dir = tempfile.mkdtemp()
-        if os.path.exists(self.test_dir):  # start clean
-            self.tearDown()
-        os.mkdir(self.test_dir)
         self.type_map = TypeMap()
 
     def tearDown(self):
diff --git a/tests/unit/common/test_table.py b/tests/unit/common/test_table.py
index 15a0c9e91..1c439248a 100644
--- a/tests/unit/common/test_table.py
+++ b/tests/unit/common/test_table.py
@@ -1285,6 +1285,34 @@ def test_no_df_nested(self):
         with self.assertRaisesWith(ValueError, msg):
             dynamic_table_region.get(0, df=False, index=False)
 
+    def test_init_out_of_bounds(self):
+        table = self.with_columns_and_data()
+        with self.assertRaises(IndexError):
+            DynamicTableRegion(name='dtr', data=[0, 1, 2, 2, 5], description='desc', table=table)
+
+    def test_init_out_of_bounds_long(self):
+        table = self.with_columns_and_data()
+        data = np.ones(DynamicTableRegion.MAX_ROWS_TO_VALIDATE_INIT+1, dtype=int)*5
+        dtr = DynamicTableRegion(name='dtr', data=data, description='desc', table=table)
+        assert dtr.data is data  # no exception raised
+
+    def test_init_out_of_bounds_no_validate(self):
+        table = self.with_columns_and_data()
+        dtr = DynamicTableRegion(name='dtr', data=[0, 1, 5], description='desc', table=table, validate_data=False)
+        self.assertEqual(dtr.data, [0, 1, 5])  # no exception raised
+
+    def test_add_row_out_of_bounds(self):
+        table = self.with_columns_and_data()
+        dtr = DynamicTableRegion(name='dtr', data=[0, 1, 2, 2], description='desc', table=table)
+        with self.assertRaises(IndexError):
+            dtr.add_row(5)
+
+    def test_set_table_out_of_bounds(self):
+        table = self.with_columns_and_data()
+        dtr = DynamicTableRegion(name='dtr', data=[0, 1, 5], description='desc')
+        with self.assertRaises(IndexError):
+            dtr.table = table
+
 
 class DynamicTableRegionRoundTrip(H5RoundTripMixin, TestCase):
 
diff --git a/tests/unit/test_io_hdf5_streaming.py b/tests/unit/test_io_hdf5_streaming.py
index 1a487b939..c03110a76 100644
--- a/tests/unit/test_io_hdf5_streaming.py
+++ b/tests/unit/test_io_hdf5_streaming.py
@@ -80,9 +80,9 @@ def setUp(self):
         self.manager = BuildManager(type_map)
 
     def tearDown(self):
-        if os.path.exists(self.ns_filename):
+        if hasattr(self, 'ns_filename') and os.path.exists(self.ns_filename):
             os.remove(self.ns_filename)
-        if os.path.exists(self.ext_filename):
+        if hasattr(self, 'ext_filename') and os.path.exists(self.ext_filename):
             os.remove(self.ext_filename)
 
     def test_basic_read(self):