In the present work, a series of substituted 4-N, N-dimethylamino and 4-carboxy chalcones were synthesized using Clasien-Schimdt condensation and characterized by spectral data. The antinociceptive activity was studied in mice using different models. The results indicated that in the 4-dimethylamino series, compound 4c, bearing 3,4-dimethoxy substituent has shown good peripheral antinociceptive activity. Among the 4-carboxy series, 5c and 5i were found to be potent both in central and peripheral pain models. In dimethylamino chalcones, compounds 4b and 4c containing 4-methoxy and 3, 4-dimethoxy groups showed good binding affinity towards iNOS, while compound 4f bearing 4-chloro substituent exhibited good binding affinity towards COX-2 enzyme. Interestingly, in the series of carboxy chalcones compound 5e containing 4-fluoro substitution demonstrated good affinity towards both iNOS and COX-2 enzymes.