Oxidative damage was induced using several different systems to study the protective effect of capsaicin (CAS) against damage caused by OH? and alkoxy radicals (RO?). Oxidation and carbonylation of bovine serum albumin (BSA) was induced by copper ions/hydrogen peroxide and 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH), respectively. Nitration of BSA was induced by hemin/nitrite/hydrogen peroxide, peroxidation of linoleic acid (LA) was induced by ferrous iron/VitC and 2,2'-azobis(2,4-di-methylvaleronitrile) (AMVN), and oxidative damage to herring sperm DNA was induced by AAPH. The results showed that 50~1000 μM CAS could significantly inhibit the oxidative cleavage of protein induced by reactive oxygen species (ROS); 10~1000 μM CAS could significantly inhibit protein carbonylation induced by OH?, protein nitration, and the formation of thiobarbituric acid reactive substances (TBARS), the final product of LA peroxidation; and 100~1000 μM CAS could significantly inhibit protein carbonylation induced by RO? and DNA oxidative cleavage. It was concluded that CAS had a strong protective effect against oxidative damage to biomolecules caused by various types of free radicals, and the protective effects exhibited a concentration-dependent manner to some degree. This study provides scientific evidence for the development and application of CAS in dietary supplements and functional foods.