diff --git a/changes/3695.bugfix.md b/changes/3695.bugfix.md
new file mode 100644
index 0000000000..a7d847e4f1
--- /dev/null
+++ b/changes/3695.bugfix.md
@@ -0,0 +1 @@
+Raise error when trying to encode :class:`numpy.dtypes.StringDType` with `na_object` set.
\ No newline at end of file
diff --git a/src/zarr/core/dtype/npy/string.py b/src/zarr/core/dtype/npy/string.py
index 41d3a60078..904280a330 100644
--- a/src/zarr/core/dtype/npy/string.py
+++ b/src/zarr/core/dtype/npy/string.py
@@ -742,6 +742,43 @@ class VariableLengthUTF8(UTF8Base[np.dtypes.StringDType]):  # type: ignore[type-
 
         dtype_cls = np.dtypes.StringDType
 
+        @classmethod
+        def from_native_dtype(cls, dtype: TBaseDType) -> Self:
+            """
+            Create an instance of this data type from a compatible NumPy data type.
+            We reject NumPy StringDType instances that have the `na_object` field set,
+            because this is not representable by the Zarr `string` data type.
+
+            Parameters
+            ----------
+            dtype : TBaseDType
+                The native data type.
+
+            Returns
+            -------
+            Self
+                An instance of this data type.
+
+            Raises
+            ------
+            DataTypeValidationError
+                If the input is not compatible with this data type.
+            ValueError
+                If the input is `numpy.dtypes.StringDType` and has `na_object` set.
+            """
+            if cls._check_native_dtype(dtype):
+                if hasattr(dtype, "na_object"):
+                    msg = (
+                        f"Zarr data type resolution from {dtype} failed. "
+                        "Attempted to resolve a zarr data type from a `numpy.dtypes.StringDType` "
+                        "with `na_object` set, which is not supported."
+                    )
+                    raise ValueError(msg)
+                return cls()
+            raise DataTypeValidationError(
+                f"Invalid data type: {dtype}. Expected an instance of {cls.dtype_cls}"
+            )
+
         def to_native_dtype(self) -> np.dtypes.StringDType:
             """
             Create a NumPy string dtype from this VariableLengthUTF8 ZDType.
diff --git a/src/zarr/core/dtype/registry.py b/src/zarr/core/dtype/registry.py
index cb9ab50044..315945cf4e 100644
--- a/src/zarr/core/dtype/registry.py
+++ b/src/zarr/core/dtype/registry.py
@@ -161,6 +161,10 @@ def match_dtype(self, dtype: TBaseDType) -> ZDType[TBaseDType, TBaseScalar]:
             raise ValueError(msg)
         matched: list[ZDType[TBaseDType, TBaseScalar]] = []
         for val in self.contents.values():
+            # DataTypeValidationError means "this dtype doesn't match me", which is
+            # expected and suppressed. Other exceptions (e.g. ValueError for a dtype
+            # that matches the type but has an invalid configuration) are propagated
+            # to the caller.
             with contextlib.suppress(DataTypeValidationError):
                 matched.append(val.from_native_dtype(dtype))
         if len(matched) == 1:
diff --git a/tests/test_dtype_registry.py b/tests/test_dtype_registry.py
index 58b14fe07a..b7ceb502b7 100644
--- a/tests/test_dtype_registry.py
+++ b/tests/test_dtype_registry.py
@@ -15,9 +15,11 @@
     get_data_type_from_json,
 )
 from zarr.core.dtype.common import unpack_dtype_json
+from zarr.core.dtype.npy.string import _NUMPY_SUPPORTS_VLEN_STRING
 from zarr.dtype import (  # type: ignore[attr-defined]
     Bool,
     FixedLengthUTF32,
+    VariableLengthUTF8,
     ZDType,
     data_type_registry,
     parse_data_type,
@@ -74,6 +76,16 @@ def test_match_dtype(
         data_type_registry_fixture.register(wrapper_cls._zarr_v3_name, wrapper_cls)
         assert isinstance(data_type_registry_fixture.match_dtype(np.dtype(dtype_str)), wrapper_cls)
 
+    @pytest.mark.skipif(not _NUMPY_SUPPORTS_VLEN_STRING, reason="requires numpy with T dtype")
+    @staticmethod
+    def test_match_dtype_string_na_object_error(
+        data_type_registry_fixture: DataTypeRegistry,
+    ) -> None:
+        data_type_registry_fixture.register(VariableLengthUTF8._zarr_v3_name, VariableLengthUTF8)  # type: ignore[arg-type]
+        dtype: np.dtype[Any] = np.dtypes.StringDType(na_object=None)  # type: ignore[call-arg]
+        with pytest.raises(ValueError, match=r"Zarr data type resolution from StringDType.*failed"):
+            data_type_registry_fixture.match_dtype(dtype)
+
     @staticmethod
     def test_unregistered_dtype(data_type_registry_fixture: DataTypeRegistry) -> None:
         """