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Background: Sodium nitrite (NaNO2) is a chemical substance used to enhance taste, add color, and keep food products fit for consumption for a longer time. NaNO2 gives rise to a negative adverse effect on male reproductive function. Odontonema cuspidatum (OC) is a natural plant that possesses antioxidant capacity. Aim: Our research evaluates the potential beneficial effect of Odontonema cuspidatum extract on the harmful effects caused by NaNO2 on the testicular tissue and sperm characteristics of male rats. Methods: Four groups with a total of forty rats: the control, the NaNO2-received group, the OC-administered group, and the fourth group received both NaNO2 and OC. All groups were administered daily for two months. Sperm characteristics, testicular antioxidant status and histopathological changes were evaluated. Results: Coadministration of NaNO2 and OC, in comparison with NaNO2 alone, contributed to a notable enhancement in acrosomal integrity, decreasing sperm abnormalities and restoring serum testosterone levels. Moreover, such coadministration reduced the oxidative stress marker, MDA, and increased SOD in testicular tissue, lowering TNF-α gene expression, and increasing the expression of P450scc and StAR genes. Additionally, the NaNO2 and OC combination decreased the testicular histopathological changes and the Caspase-3 and PCNA immunoexpression in seminiferous tubules compared with the NaNO2 group. Conclusion: The extract of Odontonema cuspidatum exhibited the ability to decrease oxidative stress and ameliorate the detrimental effects caused by NaNO2. [Open Vet J 2024; 14(1.000): 304-315]