diff --git a/doc/source/whatsnew/v2.1.2.rst b/doc/source/whatsnew/v2.1.2.rst
index 569864ba71122..cc51e22265d7c 100644
--- a/doc/source/whatsnew/v2.1.2.rst
+++ b/doc/source/whatsnew/v2.1.2.rst
@@ -16,6 +16,7 @@ Fixed regressions
 - Fixed bug where PDEP-6 warning about setting an item of an incompatible dtype was being shown when creating a new conditional column (:issue:`55025`)
 - Fixed regression in :meth:`DataFrame.join` where result has missing values and dtype is arrow backed string (:issue:`55348`)
 - Fixed regression in :meth:`DataFrame.resample` which was extrapolating back to ``origin`` when ``origin`` was outside its bounds (:issue:`55064`)
+- Fixed regression in :meth:`DataFrame.sort_index` which was not sorting correctly when the index was a sliced :class:`MultiIndex` (:issue:`55379`)
 
 .. ---------------------------------------------------------------------------
 .. _whatsnew_212.bug_fixes:
diff --git a/pandas/tests/frame/methods/test_sort_index.py b/pandas/tests/frame/methods/test_sort_index.py
index 985a9e3602410..f0222e5cec9b5 100644
--- a/pandas/tests/frame/methods/test_sort_index.py
+++ b/pandas/tests/frame/methods/test_sort_index.py
@@ -955,3 +955,42 @@ def test_sort_index_multiindex_sort_remaining(self, ascending):
             )
 
         tm.assert_frame_equal(result, expected)
+
+
+def test_sort_index_with_sliced_multiindex():
+    # GH 55379
+    mi = MultiIndex.from_tuples(
+        [
+            ("a", "10"),
+            ("a", "18"),
+            ("a", "25"),
+            ("b", "16"),
+            ("b", "26"),
+            ("a", "45"),
+            ("b", "28"),
+            ("a", "5"),
+            ("a", "50"),
+            ("a", "51"),
+            ("b", "4"),
+        ],
+        names=["group", "str"],
+    )
+
+    df = DataFrame({"x": range(len(mi))}, index=mi)
+    result = df.iloc[0:6].sort_index()
+
+    expected = DataFrame(
+        {"x": [0, 1, 2, 5, 3, 4]},
+        index=MultiIndex.from_tuples(
+            [
+                ("a", "10"),
+                ("a", "18"),
+                ("a", "25"),
+                ("a", "45"),
+                ("b", "16"),
+                ("b", "26"),
+            ],
+            names=["group", "str"],
+        ),
+    )
+    tm.assert_frame_equal(result, expected)