diff --git a/doc/source/whatsnew/v2.1.3.rst b/doc/source/whatsnew/v2.1.3.rst
index 1359123ef153e..3b1cd1c152baa 100644
--- a/doc/source/whatsnew/v2.1.3.rst
+++ b/doc/source/whatsnew/v2.1.3.rst
@@ -21,7 +21,7 @@ Fixed regressions
 
 Bug fixes
 ~~~~~~~~~
--
+- Bug in :meth:`DatetimeIndex.diff` raising ``TypeError`` (:issue:`55080`)
 -
 
 .. ---------------------------------------------------------------------------
diff --git a/pandas/core/indexes/base.py b/pandas/core/indexes/base.py
index 761f5df3bb4e0..0301830df483b 100644
--- a/pandas/core/indexes/base.py
+++ b/pandas/core/indexes/base.py
@@ -6991,7 +6991,7 @@ def infer_objects(self, copy: bool = True) -> Index:
         return result
 
     @final
-    def diff(self, periods: int = 1) -> Self:
+    def diff(self, periods: int = 1) -> Index:
         """
         Computes the difference between consecutive values in the Index object.
 
@@ -7017,7 +7017,7 @@ def diff(self, periods: int = 1) -> Self:
         Index([nan, 10.0, 10.0, 10.0, 10.0], dtype='float64')
 
         """
-        return self._constructor(self.to_series().diff(periods))
+        return Index(self.to_series().diff(periods))
 
     @final
     def round(self, decimals: int = 0) -> Self:
diff --git a/pandas/tests/indexes/test_datetimelike.py b/pandas/tests/indexes/test_datetimelike.py
index 71cc7f29c62bc..5ad2e9b2f717e 100644
--- a/pandas/tests/indexes/test_datetimelike.py
+++ b/pandas/tests/indexes/test_datetimelike.py
@@ -159,3 +159,11 @@ def test_where_cast_str(self, simple_index):
 
         result = index.where(mask, ["foo"])
         tm.assert_index_equal(result, expected)
+
+    @pytest.mark.parametrize("unit", ["ns", "us", "ms", "s"])
+    def test_diff(self, unit):
+        # GH 55080
+        dti = pd.to_datetime([10, 20, 30], unit=unit).as_unit(unit)
+        result = dti.diff(1)
+        expected = pd.TimedeltaIndex([pd.NaT, 10, 10], unit=unit).as_unit(unit)
+        tm.assert_index_equal(result, expected)