About a third of human infertility is related to male factors. Of these, idiopathic-related infertility is not curable. Diabetes mellitus is a metabolic disorder that affects male impotence and fertility by increased production of free radicals and oxidative stress. Saponin, a glycosidic compound found in many plants, improves sperm parameters. The present study investigated the effect of Saponin on sperm oxidative stress and testicular structure in streptozotocin-induced diabetic mice. The diabetes was induced by the administration of 150 mg kg-1 streptozotocin via a single intraperitoneal injection. All experimental mice were allocated to the following groups: control group, diabetic control group, diabetic group administrated 100 mg kg-1 Saponin daily, and one healthy group administrated Saponin daily for 56 days. At the end of the treatment period, serum levels of insulin, glucose, and oxidative stress markers were measured. A histological evaluation of testicles was performed. Treatment of diabetic mice with Saponin ameliorated testicular tissue damage, serum glucose, and insulin concentrations. Furthermore, in the diabetic group, the serum concentration of malondialdehyde was increased while the activity of superoxide dismutase and glutathione peroxidase enzymes was reduced. The mean Johnsen's score and the diameter and thickness of seminiferous tubules were lower in the diabetic mice than in the control group. However, these parameters were higher in the Saponin-treated mice than in the control group. Overall, Saponin administration rectified all examined parameters. The antioxidant role of Saponin improves sperm parameters and diabetes-induced testicular oxidative damage.