In the present study a series of chalcone semicarbazones was synthesized and evaluated for antioxidant activity by DPPH free radical scavenging assay. Most of the compounds were found to be potent antioxidant. Free radicals play an important role in various pathological and xenotoxic effects so antioxidant may have protective role in these pathological conditions. Based on the results of an anti-oxidant study, Compound 23 was the most active compound. The highest scavenger activity observed in compound 23 is probably due to the presence of hydroxyl group in the acetophenic moiety and methoxy group in aldehydic moiety of the chalcone. It was found that methoxy and hydroyl substituted chalcone semicarbazones were potent free radical scavenger and unsubstituted compound showed very less activity.