Type 2 diabetes (T2D) is a chronic metabolic disorder caused by defective insulin signaling, insulin resistance, and impairment of insulin secretion. Autophagy is a conserved lysosomal-dependent catabolic cellular pathway involved in the pathogenesis of T2D and its complications. Basal autophagy regulates pancreatic beta-cell function by enhancing insulin release and peripheral insulin sensitivity. Therefore, defective autophagy is associated with impairment of pancreatic beta-cell function and the development of insulin rersistance (IR). However, over-activated autophagy increases apoptosis of pancreatic beta-cells leading to pancreatic beta-cell dysfunction. Hence, autophagy plays a double-edged sword role in T2D. Therefore, the use of autophagy modulators including inhibitors and activators may affect the pathogenesis of T2D. Hence, this review aims to clarify the potential role of autophagy inhibitors and activators in T2D.