The prevalence of diabetes mellitus (DM) has been increasing worldwide. Diabetic cardiomyopathy (DCP) is the major risk for diabetes associated morbidity and mortality. Hyperglycemia and hyperinsulinemia play an indispensable role in underlying mechanisms of DCP. They increase advanced glycation end products (AGEs) following a series of events leading to myocardial damage and cardiomyopathy which include oxidative stress, increased inflammation, fibrosis, hypertrophy and apoptosis. SIRT1 is a nicotinamide adenosine dinucleotide (NAD)-dependent deacetylase that removes acetyl groups from proteins which can be implicated in DCP. SIRT1 modulate different proteins related to hyperglycemia. SIRT1 inhibits transcriptional factors, such as p300, NF-κB, P38MAPK, Histone 3, MMP-9, FOXO3a and p53. On the other hand, it increases SERCA2a, ERK1/2/Homer1, eNOS, PGC-1α and AMPK. Therefore, SIRT1 attenuate cardiac dysfunction and improve DCP. This review focus on the role of SIRT1 in diabetic cardiomyopathy.