The present study is to evaluate antiepileptic activity of methanolic extract of vitex negundo leaf on maximal electroshock (MES), Pentylenetetrazole, Strychnine, Picrotoxin and lithiumpilocarpine induced convulsions in mice. The extract protected animals against MES induced convulsions and showed potentiating effect against different chemical induced convulsions against standard drugs. Methanolic extract of vitex negundo may be interfering with inhibiting Na+ Channels and interfering with gabanergic mechanism is due to the presence of flavonoids attributed to their activity in a dose dependant manner. Screening results indicate methanolic extract of vitex negundo may be showing possible efficacy potential in the treatment of epilepsy.