Numerous epidemiological studies indicate that consumption of polyphenol-rich food and beverages is associated with a protective effect on the cardiovascular system. The beneficial effect has been attributable to several mechanisms including the improvement of the vascular function. Indeed, polyphenols have been shown to be potent stimulators of endothelial vasoprotective mechanisms including the formation of nitric oxide (NO) and the induction of endothelium-derived hyperpolarization (EDH). The aim of this review is to provide a non-exhaustive analysis of the literature regarding polyphenols-rich sources capable of activating endothelial NO synthase and the characterization of the underlying mechanism as well as the beneficial effects of polyphenols on the endothelial function in both experimental models of cardiovascular diseases and in Humans.