diff --git a/django/db/models/base.py b/django/db/models/base.py
index 36b16c11320c..d1321d654088 100644
--- a/django/db/models/base.py
+++ b/django/db/models/base.py
@@ -2220,6 +2220,20 @@ def _check_local_fields(cls, fields, option):
                             id="models.E048",
                         )
                     )
+                elif (
+                    isinstance(field.remote_field, ForeignObjectRel)
+                    and field not in cls._meta.local_concrete_fields
+                    and len(field.from_fields) > 1
+                ):
+                    errors.append(
+                        checks.Error(
+                            f"{option!r} refers to a ForeignObject {field_name!r} with "
+                            "multiple 'from_fields', which is not supported for that "
+                            "option.",
+                            obj=cls,
+                            id="models.E049",
+                        )
+                    )
                 elif field not in cls._meta.local_fields:
                     errors.append(
                         checks.Error(
diff --git a/django/db/models/indexes.py b/django/db/models/indexes.py
index 176f719fe568..a408506527b6 100644
--- a/django/db/models/indexes.py
+++ b/django/db/models/indexes.py
@@ -114,7 +114,12 @@ def check(self, model, connection):
                 )
         errors.extend(
             model._check_local_fields(
-                {*self.fields, *self.include, *references}, "indexes"
+                {
+                    *[field for field, _ in self.fields_orders],
+                    *self.include,
+                    *references,
+                },
+                "indexes",
             )
         )
         # Database-feature checks:
diff --git a/docs/ref/checks.txt b/docs/ref/checks.txt
index ab92220ac993..7735eed47898 100644
--- a/docs/ref/checks.txt
+++ b/docs/ref/checks.txt
@@ -443,6 +443,9 @@ Models
 * **models.E048**: ``constraints/indexes/unique_together`` refers to a
   ``CompositePrimaryKey`` ``<field name>``, but ``CompositePrimaryKey``\s are
   not supported for that option.
+* **models.E049**: ``constraints/indexes/unique_together`` refers to a
+  ``ForeignObject`` ``<field name>`` with multiple ``from_fields``, which is
+  not supported for that option.
 
 Management Commands
 -------------------
diff --git a/docs/releases/6.0.txt b/docs/releases/6.0.txt
index 56e4bf2315e2..fd30c66121ee 100644
--- a/docs/releases/6.0.txt
+++ b/docs/releases/6.0.txt
@@ -295,6 +295,10 @@ Models
   don't support it (MySQL and MariaDB), the fields are marked as deferred to
   trigger a refresh on subsequent accesses.
 
+* Using a :ref:`ForeignObject <cpk-and-relations>` with multiple
+  ``from_fields`` in Model indexes, constraints, or :attr:`unique_together
+  <django.db.models.Options.unique_together>` now emits a system check error.
+
 Pagination
 ~~~~~~~~~~
 
diff --git a/tests/invalid_models_tests/test_models.py b/tests/invalid_models_tests/test_models.py
index faa0db9da7bd..2a39e250bdb1 100644
--- a/tests/invalid_models_tests/test_models.py
+++ b/tests/invalid_models_tests/test_models.py
@@ -166,6 +166,54 @@ class Meta:
             ],
         )
 
+    def test_pointing_to_foreign_object(self):
+        class Reference(models.Model):
+            reference_id = models.IntegerField(unique=True)
+
+        class ReferenceTab(models.Model):
+            reference_id = models.IntegerField()
+            reference = models.ForeignObject(
+                Reference,
+                from_fields=["reference_id"],
+                to_fields=["reference_id"],
+                on_delete=models.CASCADE,
+            )
+
+            class Meta:
+                unique_together = [["reference"]]
+
+        self.assertEqual(ReferenceTab.check(), [])
+
+    def test_pointing_to_foreign_object_multi_column(self):
+        class Reference(models.Model):
+            reference_id = models.IntegerField(unique=True)
+            code = models.CharField(max_length=1)
+
+        class ReferenceTabMultiple(models.Model):
+            reference_id = models.IntegerField()
+            code = models.CharField(max_length=1)
+            reference = models.ForeignObject(
+                Reference,
+                from_fields=["reference_id", "code"],
+                to_fields=["reference_id", "code"],
+                on_delete=models.CASCADE,
+            )
+
+            class Meta:
+                unique_together = [["reference"]]
+
+        self.assertEqual(
+            ReferenceTabMultiple.check(),
+            [
+                Error(
+                    "'unique_together' refers to a ForeignObject 'reference' with "
+                    "multiple 'from_fields', which is not supported for that option.",
+                    obj=ReferenceTabMultiple,
+                    id="models.E049",
+                ),
+            ],
+        )
+
 
 @isolate_apps("invalid_models_tests")
 class IndexesTests(TestCase):
@@ -185,6 +233,15 @@ class Meta:
             ],
         )
 
+    def test_pointing_to_desc_field(self):
+        class Model(models.Model):
+            name = models.CharField(max_length=100)
+
+            class Meta:
+                indexes = [models.Index(fields=["-name"], name="index_name")]
+
+        self.assertEqual(Model.check(databases=self.databases), [])
+
     def test_pointing_to_m2m_field(self):
         class Model(models.Model):
             m2m = models.ManyToManyField("self")