diff --git a/spyder/plugins/variableexplorer/widgets/dataframeeditor.py b/spyder/plugins/variableexplorer/widgets/dataframeeditor.py
index 4098e2d867d..da26604d63e 100644
--- a/spyder/plugins/variableexplorer/widgets/dataframeeditor.py
+++ b/spyder/plugins/variableexplorer/widgets/dataframeeditor.py
@@ -63,7 +63,7 @@
 from spyder.utils.palette import QStylePalette
 
 
-# Supported Numbers and complex numbers
+# Supported real and complex number types
 REAL_NUMBER_TYPES = (float, int, np.int64, np.int32)
 COMPLEX_NUMBER_TYPES = (complex, np.complex64, np.complex128)
 
@@ -91,6 +91,18 @@
 BACKGROUND_MISC_ALPHA = 0.3
 
 
+def is_any_real_numeric_dtype(dtype) -> bool:
+    """
+    Test whether a Pandas dtype is a real numeric type.
+    """
+    try:
+        import pandas.api.types
+        return pandas.api.types.is_any_real_numeric_dtype(dtype)
+    except Exception:
+        # Pandas version 1
+        return dtype in REAL_NUMBER_TYPES
+
+
 def bool_false_check(value):
     """
     Used to convert bool entrance to false.
@@ -250,8 +262,11 @@ def max_min_col_update(self):
             # the maximum of a column.
             # Fixes spyder-ide/spyder#17145
             try:
-                if col.dtype in REAL_NUMBER_TYPES + COMPLEX_NUMBER_TYPES:
-                    if col.dtype in REAL_NUMBER_TYPES:
+                if (
+                    is_any_real_numeric_dtype(col.dtype)
+                    or col.dtype in COMPLEX_NUMBER_TYPES
+                ):
+                    if is_any_real_numeric_dtype(col.dtype):
                         vmax = col.max(skipna=True)
                         vmin = col.min(skipna=True)
                     else:
diff --git a/spyder/plugins/variableexplorer/widgets/tests/test_dataframeeditor.py b/spyder/plugins/variableexplorer/widgets/tests/test_dataframeeditor.py
index 4e5f3b0ef59..ed57af8f0d8 100644
--- a/spyder/plugins/variableexplorer/widgets/tests/test_dataframeeditor.py
+++ b/spyder/plugins/variableexplorer/widgets/tests/test_dataframeeditor.py
@@ -358,6 +358,41 @@ def test_dataframemodel_get_bgcolor_with_missings():
             'Wrong bg color for missing of type ' + column
 
 
+def test_dataframemodel_get_bgcolor_with_nullable_numbers():
+    """
+    Test background colors for nullable integer data types
+
+    Regression test for spyder-ide/spyder#21222.
+    """
+    vals = [1, 2, 3, 4, 5]
+    vals_na = [1, 2, 3, None, 5]
+    df = DataFrame({
+        'old': Series(vals),
+        'old_na': Series(vals_na),
+        'new': Series(vals, dtype='Int64'),
+        'new_na': Series(vals_na, dtype='Int64')
+    })
+    dfm = DataFrameModel(df)
+    dfm.colum_avg(0)
+
+    # Test numbers
+    h0 = dataframeeditor.BACKGROUND_NUMBER_MINHUE
+    dh = dataframeeditor.BACKGROUND_NUMBER_HUERANGE
+    s = dataframeeditor.BACKGROUND_NUMBER_SATURATION
+    v = dataframeeditor.BACKGROUND_NUMBER_VALUE
+    a = dataframeeditor.BACKGROUND_NUMBER_ALPHA
+    for col_index in range(4):
+        assert colorclose(bgcolor(dfm, 0, col_index), (h0 + dh, s, v, a))
+    assert colorclose(bgcolor(dfm, 3, 0), (h0 + 1 / 4 * dh, s, v, a))
+    assert colorclose(bgcolor(dfm, 3, 2), (h0 + 1 / 4 * dh, s, v, a))
+
+    # Test null values
+    h, s, v, __ = QColor(dataframeeditor.BACKGROUND_NONNUMBER_COLOR).getHsvF()
+    alpha = dataframeeditor.BACKGROUND_MISC_ALPHA
+    assert colorclose(bgcolor(dfm, 3, 1), (h, s, v, alpha))
+    assert colorclose(bgcolor(dfm, 3, 3), (h, s, v, alpha))
+
+
 def test_dataframemodel_with_format_percent_d_and_nan():
     """
     Test DataFrameModel with format `d` and dataframe containing NaN