Epilepsy is a neurological disorder characterized by spontaneous, recurrent and paroxysmal cerebral discharge, clinically leading to persistent alterations in function and morphology of neurons. Oxidative stress is one of possible mechanisms in the pathogenesis of epilepsy. Oxidative stress resulting from mitochondrial dysfunction gradually disrupts the intracellular calcium homeostasis, which modulates neuronal excitability and synaptic transmission making neurons more vulnerable to additional stress, and leads to neuronal loss in epilepsy. In addition, the high oxidative status is associated with the severity and recurrence of epileptic seizure. Hence, treatment with antioxidants is critically important in epileptic patients through scavenging the excessive free radicals to protect the neuronal loss. In this review, we reviewed the recent findings that focus on the role for antioxidants in prevention of mitochondrial dysfunction and the correlation between oxidative status and disease prognosis in patients with epilepsy.