Abstract: Epilepsy and its comorbidities affect the health of tens of millions of people, characterized by complex and poorly understood etiology. While anti-seizure medications (ASMs) remains the primary treatment approach, antiepileptic drugs face issues like drug resistance and severe side effects, highlighting an urgent need for novel drugs and therapeutic strategies. The gut microbiota plays a crucial role in the pathogenesis of central nervous system diseases. They can interact with the brain through the nervous, endocrine, immune and metabolic systems, thereby influencing the course of the disease. Some researches have indicated that gut microbiota-targeted interventions, such as the ketogenic diet (KD), fecal microbiota transplantation (FMT), and probiotics, demonstrate the significant potential in the treatment of epilepsy. However, there are still many unsolved mysteries regarding the role of gut bacteria in the onset and treatment of epilepsy. Investigating the regulatory role of the gut microbiota in epilepsy and its comorbidities holds great significance.