Hypertension is considered the most important risk factor in the development of cardiovascular disease. Considerable evidence suggests that oxidative stress, which results in an excessive generation of reactive oxygen species (ROS), plays a key role in the pathogenesis of hypertension. This phenomenon leads to endothelial dysfunction, an imbalance between endothelium-derived relaxing factors, such as nitric oxide (NO), and contracting factors, such as angiotensin-II and endothelin (ET)-1, favoring the latter. Vascular remodeling also takes place; both processes lead to hypertension establishment. Antioxidant therapies have been evaluated in order to decrease ROS production or increase their scavenging. In this line, polyphenols, widespread antioxidants in fruits, vegetables, and wine, have demonstrated their beneficial role in prevention and therapy of hypertension, by acting as free radical scavengers, metal chelators, and in enzyme modulation and expression. Polyphenols activate and enhance endothelial nitric oxide synthase (eNOS) expression by several signaling pathways, increase glutathione (GSH), and inhibit ROS-producing enzymes such as NADPH and xanthine oxidases. These pathways lead to improved endothelial function, subsequent normalization of vascular tone, and an overall antihypertensive effect. In practice, diets as Mediterranean and the "French paradox" phenomenon, the light and moderate red wine consumption, supplementation with polyphenols as resveratrol or quercetin, and also experimental and clinical trials applying the mentioned have coincided in the antihypertensive effect of polyphenols, either in prevention or in therapy. However, further trials are yet needed to fully assess the molecular mechanisms of action and the appearance of adverse reactions, if a more extensive recommendation of polyphenol introduction in diet wants to be made.