The antioxidant activity of Withania somnifera (WS) glycowithanolides was assessed in chronic footshock stress induced changes in rat brain frontal cortex and striatum. The stress procedure, given once daily for 21 days, induced an increase in superoxide dismutase (SOD) and lipid peroxidation (LPO) activity, with concomitant decrease in catalase (CAT) and glutathione peroxidase (GPX) activities in both the brain regions. WS glycowithanolides (WSG), administered orally 1 h prior to the stress procedure for 21 days, in the doses of 10, 20 and 50 mg/kg, induced a dose-related reversal of the stress effects. Thus, WSG tended to normalise the augmented SOD and LPO activities and enhanced the activities of CAT and GPX. The results indicate that, at least part of chronic stress-induced pathology may be due to oxidative stress, which is mitigated by WSG, lending support to the clinical use of the plant as an antistress adaptogen.