Pomegranate, a recognized source of phenolic compounds, has been associated with health-promoting benefits, mostly due to its antioxidant activity. Ellagic and gallic acids, anthocyanins, and ellagitannins are the main phenolics in pomegranate, showing antioxidant activity. For this reason, pomegranate has been used in foods, such as meat products, as an attempt to retard lipid oxidation and increase shelf-life. In recent years, in vitro, in vivo, and human studies reported the antioxidant activity of pomegranate, especially its peels, with reduced incidence of chronic diseases (e.g., cardiovascular ailments, cancer, neurodegenerative disease, type 2 diabetes, chronic kidney disease). This review aims to present the main antioxidant compounds on pomegranate and their biological effects, the antioxidant activity of pomegranate-based foods, the application of pomegranate as a natural antioxidant food additive, the role of pomegranate in the prevention and management of chronic diseases, as well as the trends and prospects regarding the application of pomegranate in innovative food and health.