Stress triggers a physiological response by increasing themetabolic rate which translates into oxidative stress, resulting in the etiopathogenesis of many diseases. Several micronutrients like antioxidant vitamins and minerals can modulate the state of oxidative stress. This study tests whether an MM (consisting of functionally diverse dietary antioxidants) compares favourably with a combination of vitamins E and C, in providing increased anti-oxidative protection against chronic unpredictable stress (CUS) induced oxidative damage in mice. Thirty-two Swiss albino mice were randomized to one of the following groups: control+vehicle, CUS+ vehicle, CUS+ MM, and CUS+ vitamins (C+E). CUS was applied for 4 weeks and MM and vitamins (C+E) were administered orally for the same period. CUS led to a negative impact on all the biochemical parameters analyzed in circulation, liver and kidney with elevation of malondialdehydeand reduction of glutathione levels. The activities of superoxide dismutase, catalase, glutathione S-transferase, and glutathione reductase were decreased by CUS, with an elevation of liver marker enzymes, glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) in the circulation and liver. Supplementation with MM and vitamins (C+E) restored the disturbed antioxidant status in the stress exposed mice. However, MM was found more effective than vitamins (C+E) in reinstating the altered parameters. The results of the study suggest that the cumulative action of diverse vitamins and minerals in an MM exert greater antioxidative effect than vitamins (C+E) in combating the CUS induced oxidative stress, thus supplementation of MM alone can be an effective measure to combat stress induced oxidative derangements both under normal and pathological conditions.