Obesity is one of the most important risk factors for various chronic diseases, especially related with environmental life style and eating habits. Obesity is also a risk factor of metabolic diseases, cardiovascular diseases, diabetes, and certain cancers. Numerous studies of calorie restriction (CR) in various organisms have shown several beneficial effects of not only decreased body fat and blood pressure, decreased inflammatory markers in plasma, increased insulin sensitivity, and improved lipid profile but also improved endothelial function, decreased oxidative damage by reducing energy flux and metabolism, and decreased ectopic fat accumulation. Furthermore, CR activates SIRT1, a nutrient-sensing deacetylase, involved in metabolic regulation and longevity. Resveratrol, as a mimetic of CR, is one of well-known sirtuin activating compounds. Resveratrol is related with longer lifespan by increasing insulin sensitivity, decreasing insulin-like growth factor-1, and increasing AMP-activated protein kinase activity. Therefore, the present review focuses on CR related with obesity and also the relationship between CR and SIRT1 in metabolic mechanism levels. Furthermore, we will introduce resveratrol, as an activator of SIRT1, and the beneficial effects of resveratrol.