diff --git a/rest_framework/serializers.py b/rest_framework/serializers.py
index 8fe284bc8..74dd34be3 100644
--- a/rest_framework/serializers.py
+++ b/rest_framework/serializers.py
@@ -1090,6 +1090,14 @@ class ModelSerializer(Serializer):
         # Determine the fields that should be included on the serializer.
         fields = {}
 
+        # If it's a ManyToMany field, and the default is None, then raises an exception to prevent exceptions on .set()
+        for field_name in declared_fields.keys():
+            if field_name in info.relations and info.relations[field_name].to_many and declared_fields[field_name].default is None:
+                raise ValueError(
+                    f"The field '{field_name}' on serializer '{self.__class__.__name__}' is a ManyToMany field and cannot have a default value of None. "
+                    "Please set an appropriate default value, such as an empty list, or remove the default."
+                )
+
         for field_name in field_names:
             # If the field is explicitly declared on the class then use that.
             if field_name in declared_fields:
diff --git a/tests/test_serializer.py b/tests/test_serializer.py
index cefa2ee38..960c663f6 100644
--- a/tests/test_serializer.py
+++ b/tests/test_serializer.py
@@ -6,12 +6,14 @@ from collections.abc import Mapping
 
 import pytest
 from django.db import models
+from django.test import TestCase
 
 from rest_framework import exceptions, fields, relations, serializers
 from rest_framework.fields import Field
 
 from .models import (
-    ForeignKeyTarget, NestedForeignKeySource, NullableForeignKeySource
+    ForeignKeyTarget, ManyToManySource, ManyToManyTarget,
+    NestedForeignKeySource, NullableForeignKeySource
 )
 from .utils import MockObject
 
@@ -64,6 +66,7 @@ class TestSerializer:
         class ExampleSerializer(serializers.Serializer):
             char = serializers.CharField()
             integer = serializers.IntegerField()
+
         self.Serializer = ExampleSerializer
 
     def test_valid_serializer(self):
@@ -774,3 +777,35 @@ class TestSetValueMethod:
         ret = {'a': 1}
         self.s.set_value(ret, ['x', 'y'], 2)
         assert ret == {'a': 1, 'x': {'y': 2}}
+
+
+class TestWarningManyToMany(TestCase):
+    def test_warning_many_to_many(self):
+        """Tests that using a PrimaryKeyRelatedField for a ManyToMany field breaks with default=None."""
+        class ManyToManySourceSerializer(serializers.ModelSerializer):
+            targets = serializers.PrimaryKeyRelatedField(
+                many=True,
+                queryset=ManyToManyTarget.objects.all(),
+                default=None
+            )
+
+            class Meta:
+                model = ManyToManySource
+                fields = '__all__'
+
+        # Instantiates with invalid data (not value for a ManyToMany field to force using the default)
+        serializer = ManyToManySourceSerializer(data={
+            "name": "Invalid Example",
+        })
+
+        error_msg = "The field 'targets' on serializer 'ManyToManySourceSerializer' is a ManyToMany field and cannot have a default value of None. Please set an appropriate default value, such as an empty list, or remove the default."
+
+        # Calls to get_fields() should raise a ValueError
+        with pytest.raises(ValueError) as exc_info:
+            serializer.get_fields()
+        assert str(exc_info.value) == error_msg
+
+        # Calls to is_valid() should behave the same
+        with pytest.raises(ValueError) as exc_info:
+            serializer.is_valid(raise_exception=True)
+        assert str(exc_info.value) == error_msg