Abstract: Sirtuins (SIRTs) are described as NAD+-dependent deacetylases, also known as class III histone deacetylases. So far, seven sirtuin genes (SIRTS 1–7) have been identified and characterized in mammals and also known to occur in bacteria and eukaryotes. SIRTs are involved in various biological processes including endocrine system, apoptosis, aging and longevity, diabetes, rheumatoid arthritis, obesity, inflammation, etc. Among them, the best characterized one is SIRT1. Actually, small molecules seem to be the most effective SIRT modulators. Flavonoids have been reported to possess many positive effects favrable for human health, while a relatively less research has been reported so far on their funcions as SIRT modulation mechanisms. In this regard, we herein aimed to focus on modulatory effects of flavonoids on SIRTs as the most common secondary metabolites in natural products. Our literature survey covering the years of 2006-2021 pointed out that flavonoids frequently interact with SIRT1 and SIRT3 followed by SIRT6. It can be also concluded that some popular flavonoid derivatives, e.g. resveratrol, quercetin, and catechin derivatives came forward in terms of SIRT modulation.