Diabetes mellitus(DM) is a systemic and complex disease with micro and macrovascular complications that result from impaired metabolic pathways and genetic susceptibilities. DM has been accepted as an epidemic worldwide during the last two decades. A substantial gap in our knowledge exists regarding the pathophysiology of this metabolic disorder despite the improved diagnostic tools and therapeutic approaches. Sirtuins are a group of NAD+ dependent enzymes that are involved in cellular homeostasis due to their deacetylating activity. In the present review, we aimed to discuss the role of associated sirtuins in the pathogenesis and treatment of diabetes mellitus. Diabetes mellitus (DM) is a systemic and complex disease with micro and macrovascular complications that result from impaired metabolic pathways and genetic susceptibilities. DM has been accepted as an epidemic worldwide during the last two decades. A substantial gap in our knowledge exists regarding the pathophysiology of this metabolic disorder despite the improved diagnostic tools and therapeutic approaches. Sirtuins are a group of NAD + dependent enzymes that are involved in cellular homeostasis due to their deacetylating activity. In the present review, we aimed to discuss the role of associated sirtuins in the pathogenesis and treatment of diabetes mellitus.