Based on the analysis of the data of scientific literature, the mechanisms of involvement of natural antioxidants in the formation of metabolic foundations of physical performance in athletes are summarized. It is shown that one of the key factors that impede increasing physical performance is oxidative stress mediated by the training loads. The mechanisms of the effect of antioxidant pharmacological drugs on the components of the process of stimulation of physical performance are discussed, and it was found that, in addition to the direct antioxidant action these substances produce the membranotropic (membranoprotective), detoxicating, immunoprotective, and cardioprotective action. It was demonstrated that the action of the above-mentioned factors, involved in the formation of metabolic foundations of physical performance and related to the antioxidant effect on the body, may be associated with other various complex changes in homeostasis. Thus, the use of antioxidant pharmacological drugs as ergogenic aids should be strictly substantiated taking into account the focus of training load, the degree of oxidative stress and its major metabolic and pathophysiological consequences for the body of an athlete.