The aim of this study was to evaluate the protective effect of broccoli sprout extract (BSE) against ovarian and renal toxicity induced by methotrexate (MTX) in female albino rats. Methotrexate, an antimetabolite frequently utilized in cancer and autoimmune diseases, has been linked to nephrotoxicity and primary ovarian insufficiency through the induction of oxidative stress and apoptosis. Because of their rich content in glucoraphanin and sulforaphane, two powerful antioxidants, broccoli sprouts were chosen. This study comprised six groups of Thirty female albino rat (180–225 g) (n = 5): (A) Control; (B) MTX, 0.15 mg/kg/week; (C) BSE, 5 mg/kg/day; (D) BSE, 7.5 mg/kg/day; and (E) MTX + BSE, at doses of 5 and 7.5 mg/kg respectively. All treatments were administered orally. The administration of MTX induced severe ovarian histological injuries, indicated by significantly reduced number of follicles, blood vessels rupture, inflammatory cell infiltration and partly fibrosis. Administration of MTX significantly increased the levels of urea and creatinine in renal tissues and induced glomerular damage such as congestion, necrosis, and cellular vacuolation. Consistent with this, these histopathological changes were prevented by simultaneous administration of BSE which appears to restore folliculogenesis and renal function parameters. In conclusion, the findings indicate that BSE strongly protects against MTX toxicity through a mechanism involving enhancement of antioxidant homeostasis. Thus, to summarise, broccoli sprout extract is a effective naturl adjuvant for mencerpt treatment in rescinding side effects on female reproductive and renal systems.