Ethanolic extract of Cissampelos pareira (L.) Hirsuta (Menispermaceae) roots have been examined in various acute and chronic ulcers in validated experimental models in rats. C. pareira extract of 25–100 mg/kg administered orally, twice daily for 5 days showed a dose-dependent, ulcer-protective effect. The extract demonstrated significant protection against 100% ethanol- (P < 0.05), aspirin- (P < 0.001), cold-restraint stress- (P < 0.01) and pylorus ligation- (P < 0.001) induced acute gastric ulcers in rats. A flavonoid Quercetin, isolated from C. pareira, showed significant antiulcer property (P < 0.05 to P < 0.001) against gastric ulcers in different acute models. In chronic ulcers induced by 50% acetic acid, C. pareira significantly (P < 0.001) reduced the ulcer index with decreased perforations after 5- and 10-day treatment. C. pareira significantly enhanced the defense factors as total hexose and sialic acid while significantly reducing the ulcer index in the lipid peroxidase product malondialdehyde in ethanol-induced ulcers.