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 four groups; group 1 was kept as control. In group 2, etoposide was administered at a dose of (20 mg/kg/day, i.p) for 5 days, while in groups 3; montelukast was given at a dose of (10mg/kg/day, p.o) and in group 4; curcumin was given at a dose of (20mg/kg/day, p.o) respectively for 21 days in both groups, during that i.p. injection of etoposide (20 mg/kg/day, i.p) was injected from day 8 through day 12 in both groups.Etoposide induced oxidative stress via significant increase in MDA level and significant decrease in GSH level as well as SOD and CAT 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 were 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, anti-inflammatory and antiapoptotic potential.