This study scrutinised the ameliorative properties of grape seed extract (GSE) in dexamethasone (DEX)-induced testicular and thyroid dysfunction associated with oxidative stress in male albino rats. Thirty-two healthy adult male albino rats were divided into four groups of eight animals each: normal, DEX control, DEX + GSE (200 mg/kg body weight) group and DEX + GSE (400 mg/kg body weight) group. The body weight gain and testes weight were assessed. Plasma testosterone and thyroid profile were determined. Testicular glucose-6-phosphate dehydrogenase (G-6-PDH), acid phosphatase (ACP), total protein and glutathione (GSH) levels, as well as catalase (CAT) activity also histopathological changes of the testis were evaluated. DEX treatment caused a significant decrease in body weight gain and weight of testes. Significant alterations in enzymatic and nonenzymatic antioxidants were observed. Moreover, a marked reduction in plasma testosterone levels and thyroid profile was observed. The administration of GSE significantly attenuated the deleterious effects of oxidative stress induced by DEX, as well as attenuated DEX-induced testicular and thyroid damage. Furthermore, DEX induced histological alterations in the testis. GSE ameliorated the injurious effects of DEX and improved the histological alterations in the testis.