The article presents the pathophysiological features of oxidative stress and the state of the antioxidant system in patients with epilepsy. The issues of lipid peroxidation, its markers, the relationship between oxidative stress, endothelial dysfunction and neuroinflammation, as well as pathomorphological changes in brain tissue in temporal lobe epilepsy and features of neuroplastic processes in these patients are considered. Epileptic seizures can act as a stressor for the body and are accompanied by activation of the hypothalamic-pituitary-adrenal system. The role of cortisol in changes in hippocampal plasticity and distant damage to the hippocampus is considered as a key link in the pathogenesis of cognitive and mental disorders as a result of focal brain lesions. Experimental and clinical data indicate an association between epilepsy and endothelial dysfunction. It has been established that epileptic seizures are accompanied by a long-term loss of the vasodilating function of the cerebral vascular endothelium, leading to a violation of their autoregulation. Data are presented on the possibility of restoring the perfusion of the epileptogenic focus during an attack, which allows some authors to consider them as a compensatory mechanism associated with improved perfusion of brain tissue and the energy status of the cell. The effects of antioxidants in the treatment of epilepsy and the role of comorbid disorders in its course are described. An opinion has been expressed about the prognostic role of oxidative stress markers in the cerebrospinal fluid in the development of pharmacoresistance in epilepsy.