The success of etoposide for the treatment of testicular cancer is limited by its undesirable side effects on reproductive system, which is generally ascribed to inflammation and oxidative stress. In the current study, the protective effects of montelukast and curcumin on etoposide-induced reproductive toxicity were investigated. Rats were divided into six groups; group 1 was kept as control. In groups 2, 3; montelukast and curcumin were administered at doses of (10 mg/kg/day) and (200 mg/Kg/day) respectively for 10 days. In group 4, etoposide was intraperitoneally administered at a single dose of 10 mg/kg, while in groups 5 and 6; etoposide and montelukast or curcumin, respectively, were given together at the same doses. Etoposide induced oxidative stress via significant increase in MDA level and significant decrease in GSH level as well as SOD and CATA activities. Montelukast and curcumin prevented these effects through antioxidant properties. In addition, the deleterious effects of etoposide on spermatogenesis, serum testosterone level, oxidative stress, ATP, mtDNA and nDNA damage as well as histopathological changes are eliminated by montelukast or curcumin treatment, notably curcumin could normalized some of these parameters. The present study showed that montelukast and curcumin can reverse toxic effects of etoposide on the reproductive system that can be contributed due to anti-oxidant, antiinflammatory and antiapoptotic potential.