• Physical inactivity can contribute to worse epilepsy pathophysiology. • Physical exercise decreases the production of pro-inflammatory biomarkers. • Physical exercise reduces the number of epileptic seizures in epilepsy. • The regular practice of physical exercise enhances the levels of BDNF. • Physical exercise can be used as a non-pharmacological treatment in epilepsy. Epilepsy is a brain disorder that leads to seizures and neurobiological, cognitive, psychological, and social consequences. Physical inactivity can contribute to worse epilepsy pathophysiology. Here, we review how physical exercise affects epilepsy physiopathology. An extensive literature search was performed and the mechanisms of physical exercise on epilepsy were discussed. The search was conducted in Scopus and PubMed. Articles with relevant information were included. Only studies written in English were considered. The regular practice of physical exercise can be beneficial for individuals with neurodegenerative diseases, such as epilepsy by decreasing the production of pro-inflammatory and stress biomarkers, increasing socialization, and reducing the incidence of epileptic seizures. Physical exercise is also capable of reducing the symptoms of depression and anxiety in epilepsy. Physical exercise can also improve cognitive function in epilepsy. The regular practice of physical exercise enhances the levels of brain-derived neuro factor (BDNF) in the hippocampi, induces neurogenesis, inhibits oxidative stress and reactive gliosis, avoids cognitive impairment, and stimulates the production of dopamine in the epileptic brain. Physical exercise is an excellent non-pharmacological tool that can be used in the treatment of epilepsy. [ABSTRACT FROM AUTHOR]