ETHNOPHARMACOLOGICAL RELEVANCE: Cyclea peltata (Lam.) Hook. f. & Thoms. (Menispermaceae), locally called 'Padathaali/Padakizhangu' is used in Ayurvedic medicine to treat peptic ulcer. AIM OF THE STUDY: To evaluate the gastric antisecretory and antiulcer activity of Cyclea peltata. MATERIALS AND METHODS: The ethanolic extract of Cyclea peltata root was used to evaluate its gastric antisecretory and antiulcer effect in the pylorus-ligated rat model and gastric lesions induced by ethanol or ethanol and indomethacin respectively in rats. The levels of gastric wall mucus, non-protein sulfhydryl groups (NP-SH), malondialdehyde, protein and catalase activity in the stomach samples of Cyclea peltata treated and control groups of rats were also quantified. RESULTS: The ethanolic extract of Cyclea peltata roots showed significant antisecretory activity as evidenced by decreased pepsin secretion, gastric juice volume and acid output in pylorus-ligated rats. Pretreatment with Cyclea peltata extract provided significant protection against the peptic ulceration caused by ethanol administered individually, or in combination with indomethacin. Our studies also revealed that pretreatment with Cyclea peltata significantly increased the gastric protein and catalase concentration of ethanol treated rats. Further, it showed significant gastroprotective effects on the stomach wall of ethanol or ethanol and indomethacin treated rats by decreasing malondialdehyde level, increasing the gastric wall mucus and non-protein sulfhydryl groups. CONCLUSION: The present findings demonstrate that Cyclea peltata ethanolic extract has potent antisecretory and antiulcer effects and justify the traditional/ethnic usage of this herb to treat peptic ulcers and consequent stomach ache.