Tramadol is a synthetic opioid analgesic used for moderate-to-severe pain structurally related to codeine and morphine, where their analgesic mechanism is a result of opioid and non-opioid mechanisms. This study was designed to evaluate the effects of Moringa oleifera leaves extract (MLE) on tramadol-induced testicular toxicity, sperm changes, testicular damage, and oxidative stress in male rats. Forty male albino rats were divided into four groups and treated for 4 weeks (group 1, as control; group 2, MLE; group 3, tramadol; group 4, MLE + tramadol). The relative body weight, relative testes weight, serum total testosterone, luteinizing hormone, follicle-stimulating hormone, sperm counts, vitality, total sperm motility, catalase, and superoxide dismutase activities were significantly decreased in tramadol-treated group when compared with the control group. In contrast, sperm abnormality, immotile sperm percent, testicular injury, and TBARS concentration in testes were significantly increased in the tramadol-treated group. In addition, histopathological examination for the tramadol-treated group has shown incomplete spermatogenesis, moderate degeneration in some seminiferous tubules with a significant decrease in the number of spermatogenic cells and depletion of Leydig cells. The administration of MLE with tramadol ameliorates the testicular toxicity, injury, sperm count, abnormalities, and oxidative stress induced by tramadol.