This research identify reduced expression of BAF60C in diabetic islets and demonstrate that altered β-cell BAF60C levels strongly influence metabolic homeostasis. Genetic loss of BAF60C in β-cells exacerbates hyperglycemia and islet dysfunction under metabolic stress, whereas β-cell–specific restoration of BAF60C produces protective effects. These findings establish BAF60C as an important regulator of β-cell integrity and disease progression in T2D.