The aim of this research is to examine the potential protective effect of Sesamum indicum L (SS) against reproductive toxicity induced by Ethylene Glycol Monomethyl Ether (EGME) in male rabbits (Oryctolagus cuniculus). Twenty-four adult rabbits were split equally into four groups (n=6): control, SS (150 mg/kg bw), EGME (150 mg/kg bw), and combined group (EGME-SS). The rabbits were orally administered the respective treatments daily for a period of four weeks. The effects on sperm biology, serum testosterone levels, and oxidative stress markers in the testicular tissue were evaluated, along with the histology of the testis and epididymis. The findings showed that EGME had a deleterious effect, as seen by a marked drop in blood testosterone levels and spermatozoa motility, concentration, and speed. Nonetheless, the testosterone concentration and sperm biology of the SS group were significantly improved. Interestingly, the EGME-SS group exhibited markers that were nearly the same as the control to the group, except for significantly higher spermatozoa concentration, highlighting the beneficial use of sesame. The EGME treatment led to an increase in lipid peroxidation levels, while concentrations of GSH, GPX, and CAT in the testes decreased in contrast control group. However, the concurrent supplementation of sesame significantly alleviated testicular GSH, GPX, and CAT concentration. Histological analysis revealed changes and damage in the testes and epididymis tissues of EGME-treated rabbits, including the absence of spermatozoa in several seminiferous tubules. In contrast, the histology of organs in the EGME-SS group showed less deterioration, indicating the preventive activity of sesame against EGME-induced toxicity.