We aimed to evaluate the renal protective capacity of Fermented Black Ginseng (FBG) and its mechanism to reduce the cisplatin-induced nephrotoxicity. Nephrotoxicity was induced by a single intraperitoneal injection of cisplatin (20 mg/kg) and treated with white ginseng (WB) and FBG (200 mg/kg/day, orally) for 4 days before cisplatin treatment. Biochemical results showed that WG and FBG pretreatment significantly reduced the increase of blood urea nitrogen (BUN) and creatinine, and histopathological changes were meaningfully ameliorated. Cisplatin increased the production of reactive oxygen species (ROS) and depletion of Glutathione (GSH) in serum and kidney, whereas, WG or FBG administration markedly down-regulated. Moreover, the expression of nuclear factor-kappaB (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 was markedly suppressed by both WB and FBG. However, FBG pretreatment was more effective than those of WG in COX-2, iNOS, and IL-6 levels. Moreover, FBG treated mice significantly up-regulated the antioxidative enzymes. In HPLC analysis, the increasing ginsenoside contents that include Rg1, Re, Rb1, Rc, Rb3, Rd, Rg3, Rk1, and Rg5 by heat-processing were greater about 5.7 fold when fermentation additionally. Taken together, FBG may be a worthful candidate for the prevention of nephrotoxicity in patients receiving cisplatin.