The aim of this study is to explore whether RT-5, one novel active ginsenosides from Ginseng, has protective effects against cisplatin (CDDP)-induced nephrotoxicity in vivo. One model of acute renal failure induced by CDDP in rats and one model of xenograft tumors of human cervical cancer in nude mice are established. Four groups are assigned: control, CDDP, RT-5, CDDP plus RT-5, in which the RT-5 is administered via oral gavage 24 h before CDDP intraperitoneal injection. The significant increase in blood urea nitrogen and creatinine are induced by CDDP treatment at 6 mg/kg, which are attenuated by pre-treated with RT-5 at 10 mg/kg. RT-5 could ameliorate CDDP-induced morphological damages in kidney by PAS staining, and reduce tubular apoptosis evaluated by TUNEL staining. Pretreatment with RT-5 notably inhibits CDDP-induced oxidative stress in kidney tissues. Interestingly, RT-5 does not interfere with the in vivo anti-cancer effects of CDDP against the growth of xenograft tumors in nude mice. These data suggest that co-treatment RT-5 with CDDP might attenuate the following nephrotoxicity without inhibiting its anti-tumor efficiency, which could provide one novel strategy for cancer treatment in clinics.