diff --git a/doc/source/whatsnew/v2.1.0.rst b/doc/source/whatsnew/v2.1.0.rst
index da95bca7fb2a6..c511626f060cb 100644
--- a/doc/source/whatsnew/v2.1.0.rst
+++ b/doc/source/whatsnew/v2.1.0.rst
@@ -370,6 +370,7 @@ Interval
 Indexing
 ^^^^^^^^
 - Bug in :meth:`DataFrame.__setitem__` losing dtype when setting a :class:`DataFrame` into duplicated columns (:issue:`53143`)
+- Bug in :meth:`DataFrame.__setitem__` with a boolean mask and :meth:`DataFrame.putmask` with mixed non-numeric dtypes and a value other than ``NaN`` incorrectly raising ``TypeError`` (:issue:`53291`)
 -
 
 Missing
diff --git a/pandas/core/frame.py b/pandas/core/frame.py
index 8f6698cab000c..e3c5f2facbe94 100644
--- a/pandas/core/frame.py
+++ b/pandas/core/frame.py
@@ -4074,7 +4074,6 @@ def _setitem_frame(self, key, value):
                 "Must pass DataFrame or 2-d ndarray with boolean values only"
             )
 
-        self._check_inplace_setting(value)
         self._check_setitem_copy()
         self._where(-key, value, inplace=True)
 
diff --git a/pandas/core/generic.py b/pandas/core/generic.py
index dd0092a58f8e7..e651ab45225c2 100644
--- a/pandas/core/generic.py
+++ b/pandas/core/generic.py
@@ -114,7 +114,6 @@
     is_bool_dtype,
     is_dict_like,
     is_extension_array_dtype,
-    is_float,
     is_list_like,
     is_number,
     is_numeric_dtype,
@@ -6201,21 +6200,6 @@ def _is_mixed_type(self) -> bool_t:
 
         return self.dtypes.nunique() > 1
 
-    @final
-    def _check_inplace_setting(self, value) -> bool_t:
-        """check whether we allow in-place setting with this type of value"""
-        if self._is_mixed_type and not self._mgr.is_numeric_mixed_type:
-            # allow an actual np.nan through
-            if (is_float(value) and np.isnan(value)) or value is lib.no_default:
-                return True
-
-            raise TypeError(
-                "Cannot do inplace boolean setting on "
-                "mixed-types with a non np.nan value"
-            )
-
-        return True
-
     @final
     def _get_numeric_data(self) -> Self:
         return self._constructor(self._mgr.get_numeric_data()).__finalize__(self)
@@ -10036,7 +10020,6 @@ def _where(
             # we may have different type blocks come out of putmask, so
             # reconstruct the block manager
 
-            self._check_inplace_setting(other)
             new_data = self._mgr.putmask(mask=cond, new=other, align=align)
             result = self._constructor(new_data)
             return self._update_inplace(result)
diff --git a/pandas/core/internals/array_manager.py b/pandas/core/internals/array_manager.py
index f04ac76998adc..75eaaa80a9961 100644
--- a/pandas/core/internals/array_manager.py
+++ b/pandas/core/internals/array_manager.py
@@ -443,10 +443,6 @@ def to_native_types(self, **kwargs) -> Self:
     def is_mixed_type(self) -> bool:
         return True
 
-    @property
-    def is_numeric_mixed_type(self) -> bool:
-        return all(is_numeric_dtype(t) for t in self.get_dtypes())
-
     @property
     def any_extension_types(self) -> bool:
         """Whether any of the blocks in this manager are extension blocks"""
diff --git a/pandas/core/internals/managers.py b/pandas/core/internals/managers.py
index 8e60bf02fed75..2a7c0536c66a4 100644
--- a/pandas/core/internals/managers.py
+++ b/pandas/core/internals/managers.py
@@ -514,10 +514,6 @@ def to_native_types(self, **kwargs) -> Self:
         """
         return self.apply("to_native_types", **kwargs)
 
-    @property
-    def is_numeric_mixed_type(self) -> bool:
-        return all(block.is_numeric for block in self.blocks)
-
     @property
     def any_extension_types(self) -> bool:
         """Whether any of the blocks in this manager are extension blocks"""
diff --git a/pandas/tests/frame/indexing/test_where.py b/pandas/tests/frame/indexing/test_where.py
index c5e1e3c02c26e..562f2fbe55c25 100644
--- a/pandas/tests/frame/indexing/test_where.py
+++ b/pandas/tests/frame/indexing/test_where.py
@@ -401,10 +401,23 @@ def test_where_none(self):
                 {"A": np.nan, "B": "Test", "C": np.nan},
             ]
         )
-        msg = "boolean setting on mixed-type"
 
-        with pytest.raises(TypeError, match=msg):
-            df.where(~isna(df), None, inplace=True)
+        orig = df.copy()
+
+        mask = ~isna(df)
+        df.where(mask, None, inplace=True)
+        expected = DataFrame(
+            {
+                "A": [1.0, np.nan],
+                "B": [None, "Test"],
+                "C": ["Test", None],
+            }
+        )
+        tm.assert_frame_equal(df, expected)
+
+        df = orig.copy()
+        df[~mask] = None
+        tm.assert_frame_equal(df, expected)
 
     def test_where_empty_df_and_empty_cond_having_non_bool_dtypes(self):
         # see gh-21947