In recent years, there has been increasing public interest in plant antioxidants, thanks to the potential anticarcinogenic and cardioprotective actions mediated by their biochemical properties. The red (or blood) orange (Citrus sinensis (L.) Osbeck) is a pigmented sweet orange variety typical of eastern Sicily (southern Italy), California, and Spain. In this paper, we discuss the main health-related properties of the red orange that include anticancer, anti-inflammatory, and cardiovascular protection activities. Moreover, the effects on health of its main constituents (namely, flavonoids, carotenoids, ascorbic acid, hydroxycinnamic acids, and anthocyanins) are described. The red orange juice demonstrates an important antioxidant activity by modulating many antioxidant enzyme systems that efficiently counteract the oxidative damage which may play an important role in the etiology of numerous diseases, such as atherosclerosis, diabetes, and cancer. The beneficial effects of this fruit may be mediated by the synergic effects of its compounds. Thus, the supply of natural antioxidant compounds through a balanced diet rich in red oranges might provide protection against oxidative damage under differing conditions and could be more effective than, the supplementation of an individual antioxidant.