In present study, a series of chalconesemicarbazones was synthesized and evaluated for their nitric oxide scavenging activity. Most of the compounds were found to be potent nitric oxide scavenger. Nitric oxide plays an important role in various pathological and xenotoxic effects so nitric oxide scavenger may have protective role in these pathological conditions. Based on the results of an anti-oxidant study, 1-[1-(2-hydroxyphenyl)-3-(4-methoxyphenyl)allylidene]- 4-(2-methylphenyl) semicarbazide (Compound 6) was the most active compound. It was found that methoxy and hydroyl substituted chalconesemicarbazones were potent nitric oxide scavenger and unsubstituted compound showed very less activity.