Epilepsy is a common chronic neurological disorder, characterized by recurrent unprovoked seizures. Antiepileptic agent’s treatment may last a lifetime in many patients. However, the long term treatment of synthetic anticonvulsant leads to various side effects. Chronic treatment of synthetic anticonvulsants like phenytoin and phenobarbital are reported to induced neurodegeneration and produce cognitive impairments. Many herbal neuroprotectives are added to overcome these problems of anticonvulsant therapy. Hence, the present work was undertaken to study the interaction of synthetic anticonvulsants like Phenytoin and Phenobarbital with herbal Neuroprotective, Acorus calamus.