Cadmium is a known industrial toxicant that accumulates in the kidney and causes oxidative damage. The present study was carried out to evaluate the attenuating effects of Annona muricata seed extracts against cadmium mediated renal toxicity in Wistar rats. Twenty-eight (28) Wistar albino rats sorted into four groups of seven rats per group were used in this study. Group A serves as the control and received distilled water orally. Group B, C, and D were administered 5 mg/kg body weight cadmium chloride with Group C and D were treated daily with 200 and 500 mg/kg body weight of ethanolic seed extract of Annona muricata  (ESEAM)respectively by oral administration while group B was left untreated for 14 days. Results obtained showed that cadmium significantly (P<0.05) increased the serum level of urea and creatinine. Oxidative stress was induced by cadmium with a significant increase in MDA level and decrease concentration in ascorbic acid, GSH, GPx, SOD, and CAT in the kidney. Efficacy of Annona muricata seed extracts against renal toxicity was evaluated in terms of biochemical estimation of enzymatic and non-enzymatic antioxidant activities, histopathological changes, and rate of lipid peroxidation. Treatment with ESEAM prevented deteriorative effects induced by Cd through a protective mechanism that involved the reduction of increased oxidative stress.