Objective: Cisplatin, a widely used chemotherapy agent, is known to induce testopathy and degeneration of the germinal epithelium (GE). Origanum vulgare L. (OV) leaf extract, due to its antioxidative properties, may alleviate such cellular damage. This experimental study was conducted to evaluate the protective and therapeutic effects of OV against cisplatin-induced testopathy. Methods: Forty-eight male Naval Medical Research Institute mice were assigned to six groups. Testopathy was induced via intraperitoneal injection of cisplatin (single dose, 1 mg/kg on day 0). OV was administered as treatment (400 mg/kg orally, 5 days per week, for 5 weeks). Phytochemical screening of OV was also performed. After the experimental period, the animals were euthanized, and both blood serum and testicular samples were collected. Total body weight and total testicular weight were measured. Histopathological examination using hematoxylin and eosin staining (to assess the gonadosomatic index [GSI]) and immunohistochemical (IHC) detection of 3β-hydroxysteroid dehydrogenase (3β-HSD) protein were conducted. Expression levels of the p53 and B-cell lymphoma 2 (Bcl-2) genes, as well as serum testosterone levels, were evaluated. Statistical analysis was performed with SPSS ver.16, and significance was set at p<0.05. Results: A phytochemical analysis of OV confirmed the presence of antioxidant compounds. Cisplatin administration resulted in significant detrimental alterations in testicular tissue (p<0.05). In animals receiving OV following cisplatin exposure, the GSI, testosterone levels, histological parameters, and total testicular weight improved toward physiological values (p<0.05). Additionally, IHC staining for 3β-HSD protein indicated regeneration of Leydig cells. Gene expression analysis showed down-regulation of p53 and up-regulation of Bcl-2 (p<0.05). Conclusion OV administration, owing to its antioxidative characteristics, shows promise as a protective phytomedicine against cisplatin-induced testopathy. OV promotes GE proliferation, enhances testosterone secretion, and modulates the expression of apoptotic genes.