Spirulina platensis is a microalgae with potent dietary phyto-antioxidant, anti-inflammatory and anti-carcinogenic properties. We investigated the mechanism of cisplatin induced hepatotoxicity and whether this natural antioxidant provided protection against cisplatin hepatotoxicity. The study was carried out in a mice model where the animals were segregated into different groups according to their treatments, e.g. control group with no treatment, cisplatin treated, cisplatin + Spirulina treated, cisplatin + vitamin C treated and cisplatin + Spirulina + vitamin C treated. The liver marker enzymes were found to be elevated following cisplatin treatment, signifying hepatotoxicity. The supplementation of Spirulina and vitamin C could effectively bring down the levels of these enzymes. Light microscopy also showed that cisplatin treatment induced liver injury and that histopathological abnormalities were prevented by Spirulina and vitamin C supplementation. This protective effect was further substantiated by the estimation of antioxidant levels and extent of lipid peroxidation in the Spirulina, vitamin C and Spirulina + vitamin C supplemented groups as compared to cisplatin alone.