In order to find novel pyrazine- and oxazole-based derivatives with potent antioxidant properties, three pyrazine-oxazole bi-heteroaryl compounds were obtained via FeCl3 promoted oxidative cross-dehydrogenative coupling reactions between pyrazine-N-oxides and 1,3-azoles. The structures of the compounds were confirmed by 1HNMR, 13CNMR and MS, and their antioxidant abilities were evaluated by inhibiting radicals induced oxidation of DNA and quenching radicals. The results showed that the three target compounds can effectively inhibit radicals induced oxidation of DNA and quench radicals, which indicated that they had strong radical scavenging properties and reduction ability and can be a potential antioxidant. The n values of the obtained compounds were 1.48, 1.78, and 1.88 in AAPH-induced oxidation of DNA. Moreover, the TBARS percentage of the target compounds in inhibiting HO? and GS? induced oxidation of DNA were 76.1% and 68.3%, 69.8% and 64.1%, 72.6% and 67.4%, respectively. Furthermore, the three compounds can scavenge ABTS ? and DPPH? radicals.