diff --git a/doc/source/whatsnew/v2.2.0.rst b/doc/source/whatsnew/v2.2.0.rst
index 9dc095e6de6ff..1bf18bfba4b84 100644
--- a/doc/source/whatsnew/v2.2.0.rst
+++ b/doc/source/whatsnew/v2.2.0.rst
@@ -310,7 +310,7 @@ Missing
 
 MultiIndex
 ^^^^^^^^^^
--
+- Bug in :meth:`MultiIndex.get_indexer` not raising ``ValueError`` when ``method`` provided and index is non-monotonic (:issue:`53452`)
 -
 
 I/O
diff --git a/pandas/core/indexes/base.py b/pandas/core/indexes/base.py
index e23887159c9c6..9017ff121976b 100644
--- a/pandas/core/indexes/base.py
+++ b/pandas/core/indexes/base.py
@@ -4011,8 +4011,8 @@ def _get_fill_indexer(
         self, target: Index, method: str_t, limit: int | None = None, tolerance=None
     ) -> npt.NDArray[np.intp]:
         if self._is_multi:
-            # TODO: get_indexer_with_fill docstring says values must be _sorted_
-            #  but that doesn't appear to be enforced
+            if not (self.is_monotonic_increasing or self.is_monotonic_decreasing):
+                raise ValueError("index must be monotonic increasing or decreasing")
             # error: "IndexEngine" has no attribute "get_indexer_with_fill"
             engine = self._engine
             with warnings.catch_warnings():
diff --git a/pandas/tests/indexes/multi/test_indexing.py b/pandas/tests/indexes/multi/test_indexing.py
index 78b2c493ec116..d86692477f381 100644
--- a/pandas/tests/indexes/multi/test_indexing.py
+++ b/pandas/tests/indexes/multi/test_indexing.py
@@ -342,6 +342,19 @@ def test_get_indexer_methods(self):
         expected = np.array([4, 6, 7], dtype=pad_indexer.dtype)
         tm.assert_almost_equal(expected, pad_indexer)
 
+    @pytest.mark.parametrize("method", ["pad", "ffill", "backfill", "bfill", "nearest"])
+    def test_get_indexer_methods_raise_for_non_monotonic(self, method):
+        # 53452
+        mi = MultiIndex.from_arrays([[0, 4, 2], [0, 4, 2]])
+        if method == "nearest":
+            err = NotImplementedError
+            msg = "not implemented yet for MultiIndex"
+        else:
+            err = ValueError
+            msg = "index must be monotonic increasing or decreasing"
+        with pytest.raises(err, match=msg):
+            mi.get_indexer([(1, 1)], method=method)
+
     def test_get_indexer_three_or_more_levels(self):
         # https://github.com/pandas-dev/pandas/issues/29896
         # tests get_indexer() on MultiIndexes with 3+ levels