In order to optimize the synthesis methods of coumarin-3-carboxylic acids and investigate their antioxidant properties, eighteen coumarin-3-carboxylic compounds were obtained via the reaction of meldrum’s acid and various salicylaldehydes without catalyst in water. The structures of the obtained compounds were confirmed by 1HNMR and 13CNMR, and the antioxidant activities were evaluated by inhibiting DNA oxidation reaction by hydroxyl radical (HO•), reductive glutathione radical (GS•) and 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH), aiming at exploring antioxidant abilities of different types and positions of the substitutes. The results showed that this approach is green and efficiently, and can tolerate substrates with diverse functional groups. The yields of the eighteen coumarin-3-carboxylic compounds were with ranged from 54.3% to 95.6%. All the compounds exhibited strong activities to protect DNA against oxidation induced by HO•, GS• and AAPH. The absorbance percentages of thiobarbituric acid reactive substances (TBARS) were 69.42%~93.39%, 75.23%~99.45% and 66.62%~97.72%, respectively. In reaction of inhibiting HO•, GS• and AAPH induced oxidation of DNA, the TBARS percentages of hydroxyl substituted compounds (compounds XV ~ XVIII) were 69.42% ~ 77.67%, 75.23% ~ 82.87% and 66.62% ~ 75.08%, respectively. The TBARS percentages of hydroxyl substituted compounds were far less than the other coumarin-3-carboxylic compounds (compounds I ~ XIV). The results indicated that hydroxyl substituted coumarin-3-carboxylic acids showed similar TBARS percentages to water-soluble vitamin E, and can be used as potential antioxidants.