Abstract: Sirtuins belong to deacetylases that are dependent on nicotinamide adenine dinucleotide (NAD) for their activity and a key regulator of many cellular functions including metabolism, cell growth, apoptosis, and genetic control of aging. There are seven different homologues of yeast silent information regulators (SIR) in mammals (SIRT1-SIRT7). SIRT3 is the only regulator associated with human longevity and SIRT3 also modulates mitochondrial acetylome, oxidative phosphorylation and creation of cellular ATP. Recent studies have shown that SIRT3 is relevant for the protection of many heart diseases. This review discusses the research progress of SIRT3 and its role in the prevention and treatment of cardiovascular diseases.