Biological macromolecules such as proteins and nucleic acids are highly prone to oxidative damage leading to a pathogenesis of many diseases. Previous studies have shown that c-phycocyanin (c-PC), a pigment found in cyanobacteria, has scavenging activities on various free radicals. In the present study, c-PC from Spirulina platensis was investigated for its protective activity against oxidative damage on plasmid DNA and erythrocyte membrane proteins. The results showed that c-PC can reduce percentages of DNA damage induced by Fenton’s reaction in a dose dependent manner. C-PC also possessed a protective effect on erythrocytes membrane protein. As demonstrated by SDS-PAGE analysis of red blood cells membrane, c-PC can prevent the degradation of red blood cell skeleton upon exposure to hydrogen peroxide. Both experiments showed that antioxidative activity of c-PC is higher than that of Trolox at the same concentration. The results suggested that c-phycocyanin may offer new therapeutic approaches for oxidative stress-mediated diseases.