The juice of whole fruits of Sicilian cultivars of prickly pear (Opuntia ficus indica (L.) Mill.) was investigated, and the contents of ascorbic acid, total polyphenols, and flavonoids were determined. In the juice, ferulic acid was the chief derivative of hydroxycinnamic acid and the mean concentration of total phenolic compounds was 746 microg/mL. The flavonoid fraction, analyzed by high-performance liquid chromatography-diode array detection, consisted of rutin and isorhamnetin derivatives. The juice showed antioxidant activity in the DPPH(*) test, probably due to the phenolic compounds that are effective radical scavengers. The preventive administration of the juice inhibited the ulcerogenic activity of ethanol in rat. Light microscopy observations showed an increase in mucus production and the restoration of the normal mucosal architecture. The juice is nutritionally interesting, and its dietary intake could provide protection against oxidative damage.