Lead is considered one of the most prevalent environmental and biologically hazardous toxicants among metallic elements. It severely affects human health and especially the male reproductive system by causing reproductive organ dysfunction leading to infertility. Natural dietary antioxidants are studied for their ability to ameliorate the cells'miscellaneous damage. The current study was designed to explore the effect of Vitis vinifera(Linn.) (grape) seed extract (GSE) on lead acetate (LA)-induced oxidative damage on testis and sperm quality in rats. Twenty-four male Wistar rats were allocated into four equal groups. Group I received distilled water; Group II received LA 50 mg/kg body weight (Bw); Group III received LA 50 mg/kg + GSE 200 mg/kg Bw; and Group IV received LA 50 mg/kg + GSE 400 mg/kg Bw (orally once a day for 28 days). After 28 days, levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx),and reduced glutathione (GSH) were estimated in the testicular tissue. The cauda of the epididymis was used to study the characteristics of the sperm, such assperm count, motility, viability, tail-coiled sperm, and morphology. The hematoxylin and eosin staining method was used to study histomorphology. Results revealed that LA induction significantly increased MDA concentrationand decreased the levels of SOD, CAT, GPx, andGSH. It also reduced the weight of the testis and testosterone hormone levels, declined the quality of sperm, and increased morphologically abnormal sperm. Moreover, LA severely altered the histomorphology of the testis, such as atrophy of the seminiferous tubule, degeneration of germinal epithelium, and increased interstitial space, compared with the control group. In GroupsIII and IV, coadministration of LA with GSE reduced the MDA concentration, preserved the antioxidant enzyme system and testosterone hormonal levels, restored the sperm characteristics, reduced the abnormal sperm, and improved histomorphological alterations in the testis compared with the LA-induced group. In conclusion, GSE has a potent natural antioxidant that provides promising protection against LA-induced testicular oxidative damage on testis and sperm quality in rats.