Chicoric acid (CA), a natural phenolic acid, has been used as a nutraceutical food ingredient due to its powerful antioxidant, anti-HIV and anti-diabetic bioactivities. CA could be partly metabolized into caffeic acid (CFA) and caftaric acid (CTA) on cytochrome P450s in rat liver microsomes. To compare the protective effects of CA and its metabolites on biomolecules and inflammatory responses, oxidative damage induced by free radicals in vitro and microglial inflammation triggered by lipopolysaccharide in BV2 cells were constructed. Results showed that CA, CTA and CFA all significantly inhibited protein degradation and carbonylation induced by hydroxyl radicals and alcoxyl radicals, and suppressed hemin/nitrite/H2O2 triggered-nitration. Moreover, CA, CTA and CFA all exerted remarkable inhibition capacities on linoleic acid and soybean lecithin liposomes peroxidation in a dose-dependent manner, and restrained the oxidation of herring sperm DNA, as well as the breakage of pBR322 plasmid DNA. Furthermore, CA and its metabolites suppressed lipopolysaccharide-induced decline of BV2 cell viability and the production of NO and ROS. However, bioactivities of CA were significantly stronger than those of its metabolites within a certain concentration range. This study provides scientific basis for the application of CA and its metabolites as nutrition and natural antioxidants.