Male infertility is a common side effect of doxorubicin (DOX) that substantially impairs the quality of life of young cancer survivors. Therefore, the current work was designed to evaluate the possible antioxidant and gonado-protective effects of Spirulina platensis (S. platensis) in DOX-treated rats. Intraperitoneal administration of DOX (3 mg/kg b.wt.) once weekly for 5 weeks significantly decreased the levels of testicular catalase, superoxide dismutase and glutathione peroxidase. Moreover, it significantly decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels, as well as sperm motility and sperm count. Additionally, DOX treatment significantly increased the testicular malondialdehyde concentration and the percent of sperm abnormalities and resulted in marked cystic dilation of seminiferous tubules with extensive separation, dissociation of germinal cells from the basement membrane and arrested spermatogenesis. Oral administration of S. platensis at a dose of 300 mg/kg daily for 5 weeks mitigated DOX-induced oxidative stress, testicular damage, hormone alterations and spermiogram abnormalities via its potent antioxidant activity. S. platensis may represent a potential therapeutic option to protect testicular tissue during DOX treatment.