Background: Available evidence suggests that 50% of couples with infertility are male related. Over 40% of these males consume alcohol which has been reported to be a reproductive toxicant causing depletions in the epithelium of seminiferous tubules hence reducing sperm counts and sperm morphology. Objective: To determine the effects of aqueous leaf extract of Telfairia occidentalis on alcohol-induced cyto-architectural changes in the testis. Methods: Aqueous leaf extract of Telfairia occidentalis (T. occidentalis) was administered by gastric gavage at a dose of 250 mg/kg and 500 mg/kg body weight daily, while 2 g/kg body weight of ethanol at 30% v/v was administered daily to mature male Sprague–Dawley rats. The experiment was in 2 phases. Phase 1 had groups A1–F1 and lasted for 4 weeks while phase 2 had groups A2–F2 and lasted 8 weeks. Parameters tested include: testicular histology, relative volume density, sperm parameters, malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione. Results: In both phases, there were depletions in the seminiferous epithelium, decreased sperm quality and increased MDA and SOD in animals that received alcohol only compared to control. Likewise, a significant increase of seminiferous epithelium of animals that received respective doses of 250 mg/kg and 500 mg/kg of T. occidentalis only compared to control. Animals that received T. occidentalis and alcohol simultaneously had a significant increase in seminiferous epithelium and sperm quality with decreased MDA level. Conclusion: T. occidentalis attenuated the deleterious effects of alcohol to the cyto-architecture of the testis, protected the seminiferous epithelium, reduced oxidative stress and promoted spermatogenesis.