Aim of present investigation was to evaluate anticonvulsant profile of Argentum Metallicum a homeopathic preparation in various models of convulsion by assessing various behavioral and biochemical parameters in laboratory animals. Anticonvulsant activity of Argentum Metallicum (30 CH, 200 CH and 1 M) was evaluated against pentylenetetrazole (PTZ), picrotoxin (PTX), strychnine (STR), isoniazid (INH) and maximal electroshock (MES) induced convulsions in mice as well as electrical kindling model in rats. The various in-vitro parameters were also determined including brain gamma amino butyric acid (GABA), nitric oxide (NO) and xanthine oxidase (XO). Diazepam and Phenytoin were used as reference anticonvulsant drugs for comparison. A single intraperitoneal injection of PTZ (90mg/kg), STR (5 mg/kg) and Isoniazid (300 mg/kg) and subcutaneous injection of PTX (3.5 mg/kg) resulted in hind-limb, tonic-clonic convulsion along with lethality in mice, whereas twice daily auricular stimulation resulted progressive severity of seizures in rats. It also significantly decreased (P < 0.001) brain GABA level in PTZ, PTX and INH model as well as significantly elevated (P < 0.001) brain NO and XO level in PTZ, PTX, INH as well as STR model. Mice treated with Argentum Metallicum (200 CH and 1 M) delayed onset of convulsion along with duration of tonic-clonic convulsions. It also significantly reduced mortality in mice. Rats treated with Argentum Metallicum (200 CH and 1 M) showed significant and dose dependant (P < 0.05 and P < 0.001) amelioration in severity of electrically kindled seizures and total number of rats seizure per group. Treatment with Argentum Metallicum (200 CH and 1 M) significantly (P < 0.01 and P < 0.001) elevated the brain GABA level and decreased brain NO and XO level in dose dependant manner. Argentum Metallicum exhibits its antiepileptic activity through GABAegic mechanism and by modulation of endogenous antioxidants like NO and XO.