diff --git a/doc/source/whatsnew/v2.0.3.rst b/doc/source/whatsnew/v2.0.3.rst
index 3da469c2e1fe6..7b6363a094d00 100644
--- a/doc/source/whatsnew/v2.0.3.rst
+++ b/doc/source/whatsnew/v2.0.3.rst
@@ -24,7 +24,7 @@ Bug fixes
 - Bug in :func:`RangeIndex.union` when using ``sort=True`` with another :class:`RangeIndex` (:issue:`53490`)
 - Bug in :func:`read_csv` when defining ``dtype`` with ``bool[pyarrow]`` for the ``"c"`` and ``"python"`` engines (:issue:`53390`)
 - Bug in :meth:`Series.str.split` and :meth:`Series.str.rsplit` with ``expand=True`` for :class:`ArrowDtype` with ``pyarrow.string`` (:issue:`53532`)
--
+- Bug in indexing methods (e.g. :meth:`DataFrame.__getitem__`) where taking the entire :class:`DataFrame`/:class:`Series` would raise an ``OverflowError`` when Copy on Write was enabled and the length of the array was over the maximum size a 32-bit integer can hold (:issue:`53616`)
 
 .. ---------------------------------------------------------------------------
 .. _whatsnew_203.other:
diff --git a/pandas/_libs/lib.pyx b/pandas/_libs/lib.pyx
index 37eede59e257d..a918cda157eb6 100644
--- a/pandas/_libs/lib.pyx
+++ b/pandas/_libs/lib.pyx
@@ -651,7 +651,7 @@ ctypedef fused int6432_t:
 
 @cython.wraparound(False)
 @cython.boundscheck(False)
-def is_range_indexer(ndarray[int6432_t, ndim=1] left, int n) -> bool:
+def is_range_indexer(ndarray[int6432_t, ndim=1] left, Py_ssize_t n) -> bool:
     """
     Perform an element by element comparison on 1-d integer arrays, meant for indexer
     comparisons
diff --git a/pandas/tests/libs/test_lib.py b/pandas/tests/libs/test_lib.py
index 383e1b81e17a7..6ad8d748d6997 100644
--- a/pandas/tests/libs/test_lib.py
+++ b/pandas/tests/libs/test_lib.py
@@ -6,6 +6,7 @@
     lib,
     writers as libwriters,
 )
+from pandas.compat import IS64
 
 from pandas import Index
 import pandas._testing as tm
@@ -248,6 +249,18 @@ def test_is_range_indexer(self, dtype):
         left = np.arange(0, 100, dtype=dtype)
         assert lib.is_range_indexer(left, 100)
 
+    @pytest.mark.skipif(
+        not IS64,
+        reason="2**31 is too big for Py_ssize_t on 32-bit. "
+        "It doesn't matter though since you cannot create an array that long on 32-bit",
+    )
+    @pytest.mark.parametrize("dtype", ["int64", "int32"])
+    def test_is_range_indexer_big_n(self, dtype):
+        # GH53616
+        left = np.arange(0, 100, dtype=dtype)
+
+        assert not lib.is_range_indexer(left, 2**31)
+
     @pytest.mark.parametrize("dtype", ["int64", "int32"])
     def test_is_range_indexer_not_equal(self, dtype):
         # GH#50592