diff --git a/CHANGES.rst b/CHANGES.rst
index 1879f11851..565c5a4574 100644
--- a/CHANGES.rst
+++ b/CHANGES.rst
@@ -14,6 +14,11 @@ API changes
 Service fixes and enhancements
 ------------------------------
 
+mast
+^^^^
+
+- Filtering by file extension or by a string column is now case-insensitive in ``MastMissions.filter_products``
+  and ``Observations.filter_products``. [#3427]
 
 
 Infrastructure, Utility and Other Changes and Additions
diff --git a/astroquery/mast/missions.py b/astroquery/mast/missions.py
index 82ed5c3218..ba87307d30 100644
--- a/astroquery/mast/missions.py
+++ b/astroquery/mast/missions.py
@@ -517,12 +517,7 @@ def filter_products(self, products, *, extension=None, **filters):
 
         # Filter by file extension, if provided
         if extension:
-            extensions = [extension] if isinstance(extension, str) else extension
-            ext_mask = np.array(
-                [not isinstance(x, np.ma.core.MaskedConstant) and any(x.endswith(ext) for ext in extensions)
-                 for x in products["filename"]],
-                dtype=bool
-            )
+            ext_mask = utils.apply_extension_filter(products, extension, 'filename')
             filter_mask &= ext_mask
 
         # Apply column-based filters
diff --git a/astroquery/mast/observations.py b/astroquery/mast/observations.py
index 0c73a5c124..320af9ed78 100644
--- a/astroquery/mast/observations.py
+++ b/astroquery/mast/observations.py
@@ -594,12 +594,7 @@ def filter_products(self, products, *, mrp_only=False, extension=None, **filters
 
         # Filter by file extension, if provided
         if extension:
-            extensions = [extension] if isinstance(extension, str) else extension
-            ext_mask = np.array(
-                [not isinstance(x, np.ma.core.MaskedConstant) and any(x.endswith(ext) for ext in extensions)
-                 for x in products["productFilename"]],
-                dtype=bool
-            )
+            ext_mask = utils.apply_extension_filter(products, extension, 'productFilename')
             filter_mask &= ext_mask
 
         # Apply column-based filters
diff --git a/astroquery/mast/tests/test_mast.py b/astroquery/mast/tests/test_mast.py
index 8c1f07147f..4b1613f4fb 100644
--- a/astroquery/mast/tests/test_mast.py
+++ b/astroquery/mast/tests/test_mast.py
@@ -428,7 +428,7 @@ def test_missions_filter_products(patch_post):
     assert all(~((filtered['size'] >= 14400) & (filtered['size'] <= 17280)))
 
     # Negate a string match
-    filtered = mast.MastMissions.filter_products(products, category='!CALIBRATED')
+    filtered = mast.MastMissions.filter_products(products, category='!calibrated')
     assert all(filtered['category'] != 'CALIBRATED')
 
     # Negate one string in a list
@@ -798,7 +798,7 @@ def test_observations_get_product_list(patch_post):
 def test_observations_filter_products(patch_post):
     products = mast.Observations.get_product_list('2003738726')
     filtered = mast.Observations.filter_products(products,
-                                                 productType=["SCIENCE"],
+                                                 productType=["sCiEnCE"],
                                                  mrp_only=False)
     assert isinstance(filtered, Table)
     assert len(filtered) == 7
@@ -808,8 +808,10 @@ def test_observations_filter_products(patch_post):
     assert all(filtered['productGroupDescription'] == 'Minimum Recommended Products')
 
     # Filter by extension
-    filtered = mast.Observations.filter_products(products, extension='fits')
+    filtered = mast.Observations.filter_products(products, extension='FITS')
     assert len(filtered) > 0
+    filtered = mast.Observations.filter_products(products, extension=['png'])
+    assert len(filtered) == 0
 
     # Numeric filtering
     filtered = mast.Observations.filter_products(products, size='<50000')
diff --git a/astroquery/mast/utils.py b/astroquery/mast/utils.py
index fa3ff17f71..e74973e2b7 100644
--- a/astroquery/mast/utils.py
+++ b/astroquery/mast/utils.py
@@ -445,6 +445,38 @@ def remove_duplicate_products(data_products, uri_key):
     return unique_products
 
 
+def apply_extension_filter(products, extension, filename_key):
+    """
+    Applies an extension filter to a product table.
+
+    Parameters
+    ----------
+    products : `~astropy.table.Table`
+        The product table to filter.
+    extension : str
+        The extension to filter by (e.g., 'fits', 'csv').
+    filename_key : str
+        The column name representing the filename of a product.
+
+    Returns
+    -------
+    ext_mask : `numpy.ndarray`
+        A boolean mask indicating which rows of the product table have the specified extension.
+    """
+    # Normalize extensions to lowercase
+    extensions = [extension] if isinstance(extension, str) else extension
+    extensions = tuple(ext.lower() for ext in extensions)
+
+    # Build mask
+    ext_mask = np.array(
+        [not isinstance(x, np.ma.core.MaskedConstant)
+         and str(x).lower().endswith(extensions)
+         for x in products[filename_key]],
+        dtype=bool
+    )
+    return ext_mask
+
+
 def _combine_positive_negative_masks(mask_funcs):
     """
     Combines a list of mask functions into a single mask according to:
@@ -571,7 +603,9 @@ def apply_column_filters(products, filters):
                 v = val[1:] if is_negated else val
 
                 def func(col, v=v):
-                    return np.isin(col, [v])
+                    # Normalize both column values and filter to lowercase strings for case-insensitive comparison
+                    col_lower = np.char.lower(col.astype(str))
+                    return np.isin(col_lower, [v.lower()])
                 mask_funcs.append((func, is_negated))
 
             this_mask = _combine_positive_negative_masks(mask_funcs)(col_data)