Effect of 50% ethanolic extract of Rubia cordifolia Linn was evaluated for anti-stress activity against a battery of tests such as hypoxia time, anti-fatigue effects, and cold swimming induced gastric ulceration, hypothermia and biochemical changes in the adrenal glands. This bioactive fraction exhibited significant anti-stress activity in a dose-related manner in all the parameters studied. The drug increased the physical endurance (increased survival time) of swimming mice, prevented stress-induced ulcer in rats. The result of the study indicated that 50% ethanolic extract of R. cordifolia induces a state of non-specific increased resistance against a variety of stress-induced biological changes in animals. © 2019 Elsevier B.V., All rights reserved.