diff --git a/pkg/services/ngalert/notifier/alertmanager_config.go b/pkg/services/ngalert/notifier/alertmanager_config.go
index 90d548d5e6c..cf500c86419 100644
--- a/pkg/services/ngalert/notifier/alertmanager_config.go
+++ b/pkg/services/ngalert/notifier/alertmanager_config.go
@@ -156,6 +156,13 @@ func (moa *MultiOrgAlertmanager) gettableUserConfigFromAMConfigString(ctx contex
 }
 
 func (moa *MultiOrgAlertmanager) ApplyAlertmanagerConfiguration(ctx context.Context, org int64, config definitions.PostableUserConfig) error {
+	// We cannot add this validation to PostableUserConfig as that struct is used for both
+	// Grafana Alertmanager (where inhibition rules are not supported) and External Alertmanagers
+	// (including Mimir) where inhibition rules are supported.
+	if len(config.AlertmanagerConfig.InhibitRules) > 0 {
+		return errors.New("inhibition rules are not supported")
+	}
+
 	// Get the last known working configuration
 	_, err := moa.configStore.GetLatestAlertmanagerConfiguration(ctx, org)
 	if err != nil {
diff --git a/pkg/tests/api/alerting/api_admin_configuration_test.go b/pkg/tests/api/alerting/api_admin_configuration_test.go
index 7ceae36e0b0..ed601c60ff2 100644
--- a/pkg/tests/api/alerting/api_admin_configuration_test.go
+++ b/pkg/tests/api/alerting/api_admin_configuration_test.go
@@ -10,11 +10,13 @@ import (
 	"testing"
 	"time"
 
-	"github.com/grafana/grafana/pkg/expr"
+	"github.com/prometheus/alertmanager/config"
+	"github.com/prometheus/alertmanager/pkg/labels"
 	"github.com/prometheus/common/model"
 	"github.com/stretchr/testify/require"
 
 	"github.com/grafana/grafana/pkg/components/simplejson"
+	"github.com/grafana/grafana/pkg/expr"
 	"github.com/grafana/grafana/pkg/services/datasources"
 	apimodels "github.com/grafana/grafana/pkg/services/ngalert/api/tooling/definitions"
 	ngmodels "github.com/grafana/grafana/pkg/services/ngalert/models"
@@ -352,3 +354,49 @@ func TestIntegrationAdminConfiguration_SendingToExternalAlertmanagers(t *testing
 		}, 16*time.Second, 8*time.Second) // the sync interval is 2s so after 8s all alertmanagers (if any) most probably are started
 	}
 }
+
+func TestIntegrationAdminConfiguration_CannotCreateInhibitionRules(t *testing.T) {
+	testinfra.SQLiteIntegrationTest(t)
+	dir, path := testinfra.CreateGrafDir(t, testinfra.GrafanaOpts{
+		DisableLegacyAlerting: true,
+		EnableUnifiedAlerting: true,
+		AppModeProduction:     true,
+	})
+	grafanaListedAddr, store := testinfra.StartGrafana(t, dir, path)
+	createUser(t, store, user.CreateUserCommand{
+		DefaultOrgRole: string(org.RoleAdmin),
+		Password:       "admin",
+		Login:          "admin",
+	})
+	client := newAlertingApiClient(grafanaListedAddr, "admin", "admin")
+
+	cfg := apimodels.PostableUserConfig{
+		AlertmanagerConfig: apimodels.PostableApiAlertingConfig{
+			Config: apimodels.Config{
+				Route: &apimodels.Route{
+					Receiver: "test",
+				},
+				InhibitRules: []config.InhibitRule{{
+					SourceMatchers: config.Matchers{{
+						Type:  labels.MatchEqual,
+						Name:  "foo",
+						Value: "bar",
+					}},
+					TargetMatchers: config.Matchers{{
+						Type:  labels.MatchEqual,
+						Name:  "bar",
+						Value: "baz",
+					}},
+				}},
+			},
+			Receivers: []*apimodels.PostableApiReceiver{{
+				Receiver: config.Receiver{
+					Name: "test",
+				},
+			}},
+		},
+	}
+	ok, err := client.PostConfiguration(t, cfg)
+	require.False(t, ok)
+	require.EqualError(t, err, "inhibition rules are not supported")
+}
diff --git a/pkg/tests/api/alerting/testing.go b/pkg/tests/api/alerting/testing.go
index 271546ee67a..7d3bb10aed8 100644
--- a/pkg/tests/api/alerting/testing.go
+++ b/pkg/tests/api/alerting/testing.go
@@ -3,6 +3,7 @@ package alerting
 import (
 	"bytes"
 	"encoding/json"
+	"errors"
 	"fmt"
 	"io"
 	"net/http"
@@ -341,6 +342,39 @@ func (a apiClient) UpdateAlertRuleOrgQuota(t *testing.T, orgID int64, limit int6
 	assert.Equal(t, http.StatusOK, resp.StatusCode)
 }
 
+func (a apiClient) PostConfiguration(t *testing.T, c apimodels.PostableUserConfig) (bool, error) {
+	t.Helper()
+
+	b, err := json.Marshal(c)
+	require.NoError(t, err)
+
+	u := fmt.Sprintf("%s/api/alertmanager/grafana/config/api/v1/alerts", a.url)
+	req, err := http.NewRequest(http.MethodPost, u, bytes.NewReader(b))
+	require.NoError(t, err)
+	req.Header.Set("Content-Type", "application/json")
+	client := &http.Client{}
+	resp, err := client.Do(req)
+	require.NoError(t, err)
+	require.NotNil(t, resp)
+
+	defer func() {
+		_ = resp.Body.Close()
+	}()
+	b, err = io.ReadAll(resp.Body)
+	require.NoError(t, err)
+
+	data := struct {
+		Message string `json:"message"`
+	}{}
+	require.NoError(t, json.Unmarshal(b, &data))
+
+	if resp.StatusCode == http.StatusAccepted {
+		return true, nil
+	}
+
+	return false, errors.New(data.Message)
+}
+
 func (a apiClient) PostRulesGroupWithStatus(t *testing.T, folder string, group *apimodels.PostableRuleGroupConfig) (apimodels.UpdateRuleGroupResponse, int, string) {
 	t.Helper()
 	buf := bytes.Buffer{}