A series of novel chalcone incorporated hydrazide derivatives was synthesized and characterized by elemental and spectral studies. The newly synthesized chaclones incorporated hydrazides were screened for anticonvulsant activity against maximal electroshock seizure (MES) model in male wistar rats and compared with the standard drug phenytoin. Compound N'-(3-(4-(dimethylamino)phenyl)-1-(4-fluorophenyl)allylidene)-2-phenoxybenzohydrazide 3h was found to be most active compound as comparable to standard drug phenytoin. From the in-silico neurotoxicity study, the compound 3h was found to lack of neurotoxicity.