The water extracts of Samultang (Samul) has been used for treatment of ischemic heart and brain damage in Oriental traditional medicine. However, little is known about the mechanism by which the water extract of Samul rescues cells from oxidative damages in cisplatin-induced ototoxicity. Cisplatin is a widely used chemotherapeutic agent that is also highly ototoxic. This study was designed to investigate the protective effects of Samul on ciplatin-induced ototoxicity in HEI-OC1 auditory cells and organ of Corti explant culture. Cisplatin markedly decreased the viability of HEI-OC1 auditory cells. However, treatment of HEI-OC1 cells with Samul significantly reduced cisplatin-induced cell death and apoptotic characteristics through reduction of intracellular peroxide generation. Cisplatin induced cytotoxicity in isolated and cultured hair cell progenitors from postnatal rat cochleae. These progenitor cells are isolated from the lesser epithelial ridge (LER, or outer spiral sulcus cell) area of pre-plated neonatal rat cochlear segments. However, Samul completely protected the morphological changes of organ of Corti and LER. Taken together, these data suggest that the protective effects of the water extracts of Samul against cisplatin may be mediated by the reduction of intracellular peroxide generation.