In search of novel gastroprotective agents, mangiferin, a naturally occurring glucosylxanthone from Mangifera indica L. (Anacardiaceae), was evaluated in mice on gastric injury induced by ethanol and indomethacin. The effects of mangiferin on gastric mucosal damage were assessed by determination of changes in mean gastric lesion area or ulcer score in mice and on gastric secretory volume and total acidity in 4-h pylorus-ligated rats. Mangiferin (3, 10 and 30 mg/kg, P. O.) significantly attenuated the gastric damage induced by ethanol by 30, 35, and 63 %, and of indomethacin by 22, 23 and 57 %, respectively. N-Acetylcysteine (750 mg/kg, I. P.) and lansoprazole (30 mg/kg, P. O.) used as positive controls in these ulcerogenic models resulted in 50 % and 76 % suppression of gastric injury, respectively. In 4-h pylorus-ligated rats, intraduodenally applied mangiferin (30 mg/kg) caused significant diminutions in gastric secretory volume and total acidity. In addition, like N-acetylcysteine, a donor of sulfhydryls, mangiferin effectively prevented the ethanol-associated depletion of gastric mucosal non-protein sulfhydryl content in mice, suggesting an antioxidant action. These findings provide evidence that mangiferin affords gastroprotection against gastric injury induced by ethanol and indomethacin most possibly through the antisecretory and antioxidant mechanisms of action.