diff --git a/doc/release/upcoming_changes/22357.improvement.rst b/doc/release/upcoming_changes/22357.improvement.rst
new file mode 100644
index 000000000000..a0332eaa07ba
--- /dev/null
+++ b/doc/release/upcoming_changes/22357.improvement.rst
@@ -0,0 +1,6 @@
+``numpy.typing`` protocols are now runtime checkable
+----------------------------------------------------
+
+The protocols used in `~numpy.typing.ArrayLike` and `~numpy.typing.DTypeLike`
+are now properly marked as runtime checkable, making them easier to use for
+runtime type checkers.
diff --git a/numpy/_typing/_array_like.py b/numpy/_typing/_array_like.py
index 2e5684b0bfb6..67d67ce19c31 100644
--- a/numpy/_typing/_array_like.py
+++ b/numpy/_typing/_array_like.py
@@ -3,7 +3,7 @@
 # NOTE: Import `Sequence` from `typing` as we it is needed for a type-alias,
 # not an annotation
 from collections.abc import Collection, Callable
-from typing import Any, Sequence, Protocol, Union, TypeVar
+from typing import Any, Sequence, Protocol, Union, TypeVar, runtime_checkable
 from numpy import (
     ndarray,
     dtype,
@@ -33,10 +33,12 @@
 # array.
 # Concrete implementations of the protocol are responsible for adding
 # any and all remaining overloads
+@runtime_checkable
 class _SupportsArray(Protocol[_DType_co]):
     def __array__(self) -> ndarray[Any, _DType_co]: ...
 
 
+@runtime_checkable
 class _SupportsArrayFunc(Protocol):
     """A protocol class representing `~class.__array_function__`."""
     def __array_function__(
@@ -146,7 +148,7 @@ def __array_function__(
 # Used as the first overload, should only match NDArray[Any],
 # not any actual types.
 # https://github.com/numpy/numpy/pull/22193
-class _UnknownType: 
+class _UnknownType:
     ...
 
 
diff --git a/numpy/_typing/_dtype_like.py b/numpy/_typing/_dtype_like.py
index b705d82fdb07..e92e17dd20cf 100644
--- a/numpy/_typing/_dtype_like.py
+++ b/numpy/_typing/_dtype_like.py
@@ -8,6 +8,7 @@
     TypeVar,
     Protocol,
     TypedDict,
+    runtime_checkable,
 )
 
 import numpy as np
@@ -80,6 +81,7 @@ class _DTypeDict(_DTypeDictBase, total=False):
 
 
 # A protocol for anything with the dtype attribute
+@runtime_checkable
 class _SupportsDType(Protocol[_DType_co]):
     @property
     def dtype(self) -> _DType_co: ...
diff --git a/numpy/_typing/_nested_sequence.py b/numpy/_typing/_nested_sequence.py
index 7c12c4a873db..6e9dded44530 100644
--- a/numpy/_typing/_nested_sequence.py
+++ b/numpy/_typing/_nested_sequence.py
@@ -8,6 +8,7 @@
     overload,
     TypeVar,
     Protocol,
+    runtime_checkable,
 )
 
 __all__ = ["_NestedSequence"]
@@ -15,6 +16,7 @@
 _T_co = TypeVar("_T_co", covariant=True)
 
 
+@runtime_checkable
 class _NestedSequence(Protocol[_T_co]):
     """A protocol for representing nested sequences.
 
diff --git a/numpy/typing/tests/test_runtime.py b/numpy/typing/tests/test_runtime.py
index 5b5df49dc571..44d069006320 100644
--- a/numpy/typing/tests/test_runtime.py
+++ b/numpy/typing/tests/test_runtime.py
@@ -3,11 +3,19 @@
 from __future__ import annotations
 
 import sys
-from typing import get_type_hints, Union, NamedTuple, get_args, get_origin
+from typing import (
+    get_type_hints,
+    Union,
+    NamedTuple,
+    get_args,
+    get_origin,
+    Any,
+)
 
 import pytest
 import numpy as np
 import numpy.typing as npt
+import numpy._typing as _npt
 
 
 class TypeTup(NamedTuple):
@@ -80,3 +88,26 @@ def test_keys() -> None:
     keys = TYPES.keys()
     ref = set(npt.__all__)
     assert keys == ref
+
+
+PROTOCOLS: dict[str, tuple[type[Any], object]] = {
+    "_SupportsDType": (_npt._SupportsDType, np.int64(1)),
+    "_SupportsArray": (_npt._SupportsArray, np.arange(10)),
+    "_SupportsArrayFunc": (_npt._SupportsArrayFunc, np.arange(10)),
+    "_NestedSequence": (_npt._NestedSequence, [1]),
+}
+
+
+@pytest.mark.parametrize("cls,obj", PROTOCOLS.values(), ids=PROTOCOLS.keys())
+class TestRuntimeProtocol:
+    def test_isinstance(self, cls: type[Any], obj: object) -> None:
+        assert isinstance(obj, cls)
+        assert not isinstance(None, cls)
+
+    def test_issubclass(self, cls: type[Any], obj: object) -> None:
+        if cls is _npt._SupportsDType:
+            pytest.xfail(
+                "Protocols with non-method members don't support issubclass()"
+            )
+        assert issubclass(type(obj), cls)
+        assert not issubclass(type(None), cls)