The inhibitors of advanced glycation endproduct and oxidative stress, as well as N-methyl-d-aspartate (NMDA) receptor antagonists have received considerable interest because of their close association with renoprotective effects. The therapeutic potential of 20(S)-ginsenoside Rg(3) (20(S)-Rg(3)), isolated from Panax ginseng, against streptozotocin-induced diabetic renal damage, was investigated in this study. The diabetic rats received 5, 10, and 20 mg/kg body weight/day of 20(S)-Rg(3) orally via gavage for fifteen consecutive days. The physiological abnormalities such as increases in water intake and urine volume of diabetic rats were significantly decreased by the 20 mg/kg body weight of 20(S)-Rg(3) administration. The elevated serum glucose, glycosylated protein, and thiobarbituric acid-reactive substance levels in diabetic rats were also significantly reduced by the 20(S)-Rg(3) administrations. Moreover, the renal dysfunction of diabetic rats was significantly ameliorated by the 20(S)-Rg(3) administrations in a dose-dependent manner. These beneficial effects on diabetic renal damage were related to the inhibitory effect of 20(S)-Rg(3) against NMDA receptor-mediated nitrosative stress.