Considering drug-induced lipid peroxidation as a possible mediator of drug-induced toxicity and exploiting the free radical scavenging action of antioxidants, the present study was designed to evaluate the protective effects of ascorbic acid (AA) and water extract of Spirulina plantesis (SP) to minimize 5-fluorouracil (5-FU)-induced lipid peroxidation. The study has been performed in vitro using goat liver as an experimental model. This evaluation was done by measuring the malondialdehyde (MDA), reduced glutathione (GSH), 4-hydroxy-2-nonenal (4-HNE) and nitric oxide (NO) content of the tissue as markers of lipid peroxidation. The results suggest that ascorbic acid and water extract of Spirulina plantesis could suppress the 5-FU-induced lipid peroxidation to a significant extent.