Introduction: Lead is the most ubiquitous hazardous toxin in the environment. It’s a severe threat to public health and especially to the male reproductive system. In recent years, the usage of the antioxidant to reduce the toxicity of heavy metals has expanded globally. Antioxidants can prevent or minimise the oxidation of other molecules by ROS in a tissue or cell. Grape seeds are natural, rich sources of antioxidant compounds. Aim/Objective: The present study was undertaken to investigate the effect of GSE (grape seed extract) against lead acetate-induced testicular oxidative damage on testis of Wistar rats. Materials and Methods: 24 male Wistar rats were used in the study. They were split into two groups: Group I was the control group (6 rats), and Group II had 18 rats that were given LA at 50 mg/kg BW for 28 days. On the 28th day, all 18 rats were subdivided into three groups: Group II(a) (LA Cessation), Group II(b), and Group II(c) treated with GSE once a day, orally, up to the 56th day. A preliminary phytochemical analysis was conducted. The testicular weight, enzymatic and non- enzymatic oxidative stress markers were estimated. Results: The phytochemical screening showed that bioactive compounds present in the GSE, including phenols, tannins, flavonoids, anthocyanin, glycosides, triterpenoids, and alkaloids. In addition, there was a significant decrease in SOD, CAT, GPx, and GSH levels and a significantly elevated MDA concentration. However, post-treatment with GSE significantly restored the testicular oxidative damage caused by LA in the testis. Conclusion: We concluded that the GSE may have the potential to provide a promising therapeutic effect against LA-induced testicular toxicity.