Cadmium (Cd) is a toxic heavy metal that is widespread and nephrotoxic, but the mechanism of its toxicity is not well understood. Alpha-lipoic acid (α-LA) has a protective effect on Cd-induced oxidative stress, but the underlying mechanism is also not clear. This study aimed to confirm that Cd causes renal damage and to explore the potential underlying mechanism of α-LA to the kidney. Rats were randomly divided into four groups: control group, Cd group (50 mg/L CdAc2), Cd+α-LA group (50 mg/L CdAc2 + 50 mg/kg body wt/day α-LA), and α-LA group (50 mg/kg body wt/day). The rats were exposed to Cd via drinking water and α-LA in the form of gavage at the same time every day. After 12 weeks, the activity of antioxidant enzymes and the level of Cd in the kidney were analyzed. Renal damage was evaluated based on histopathological and ultrastructure examinations. The apoptosis index was determined based on the results of western blotting and qRT-PCR. Our results indicate that accumulation of Cd causes serious kidney damage and α-LA has a protective effect against Cd-induced oxidative stress and apoptosis. Further, the findings indicate that the antioxidant, Cd chelation, and antiapoptotic activities of α-LA are the key factors that alleviate nephrotoxicity.