The purpose of the present study to evaluate the antioxidant and nephroprotective effects of N-acetylcysteine (NAC) and/or Vitamin E (Vit E) against renal damage induced by acrylamide (ACR) in rats. The antioxidant and nephroprotective efficacy of NAC and Vit E against ACR-induced nephrotoxicity in rats was investigated in this work. The rats were assigned to equal seven groups (n=7): control vehicle group (saline only), NAC group (150 mg/kg, orally), Vit E group (100 mg/kg, orally), ACR group (20 mg/kg, orally), NAC+ACR group, Vit E+ACR group, and NAC+Vit E+ACR group and all treatments were given for 30 days. Creatinine, urea, and glucose concentrations in the blood were increased as a result of ACR administration. Furthermore, ACR reduced protein and albumin levels. Malondialdehyde levels in kidney tissues were increased dramatically and reduced glutathione, superoxide dismutase, and catalase levels were decreased. ACR also caused certain degenerative lesions in the kidney tissues and elevated caspase-3 expression. On conclusion: administration of NAC and Vit E alone or in combinations ameliorated the renal toxicity and apoptosis induced by ACR.