Background: One the ways to deal with the adverse effects of oxidative stress caused by exercise activities is to use oral antioxidant supplements or to apply natural remedies. Sesamin is the most prominent lignan compound found in sesame seeds, one of the two highest sources of lignans in the human diet (the other being flax). Sesamin is catered to be a nutritional supplement that confers antioxidant and anti-inflammatory effects or possibly being an estrogen receptor modulator and fat burner. For this purpose, the present study was conducted to evaluate the effect of 10 weeks supplementation of sesamin and aerobic exercise on plasma levels of total antioxidant capacity and glutathione peroxidase in athletic men. Methods: In this quasi-experimental study, in Azarbayjan Shahid Madani University of Tabriz City from January to March of 2016 ,40 male subjects aged between 25 and 20 were randomly selected from placebo (10 subjects) and aerobic exercise (10 students), aerobic training+sesamin (10 people) and sesamin (10 people). The aerobic exercise protocol is (ten weeks / three days / 30-35 minutes). Blood samples were collected from subjects in six stages to evaluate the considered variables. Measurement of levels of antioxidant capacity and glutathione peroxidase measurements were conducted by the Antioxidant capacity and GPX assay kit (ZellBio, German). For data analysis, repeated measures of variance analysis at a significant level of 5 hundredths were used by employing SPSS software, version 20 (SPSS Inc., Chicago, IL, USA). Results: Subjects who took sesamin supplementation and performed aerobic exercise showed a significant difference in the levels of total antioxidant and glutathione peroxidase capacity in the groups (P<0.05). Also, the changes in total antioxidant and peroxide levels after interference (steps 4, 5, 6) and before interference (steps 1, 2, 3) had meaningful differences in obtained results (P=0.001). Also, the interactive effects of group and time on total antioxidant capacity and glutathione peroxidase were also significant (P=0.001). Conclusion: Aerobic exercise and supplementation of sesamin is an effective method to improve the health of mens athlete's immune system. In addition, combining supplementation with aerobic exercise can increase some of the beneficial effects of exercise during a 10-week period.