Drug-resistant epilepsy (DRE) is a chronic brain disorder that is difficult to effectively control with antiepileptic drugs, accounting for nearly one-third of the global epilepsy patient population. Recent studies have revealed significant differences in the gut microbiota (GM) composition between DRE patients and healthy individuals, suggesting that the gut microbiota may influence and regulate neurotransmitter metabolism, inflammatory responses, and blood-brain barrier function through the microbiota-gut-brain axis (MGBA), thereby participating in the modulation of seizure activity. This article systematically reviews the research progress on the mechanisms underlying the regulation of gut microbiota for the treatment of DRE, aiming to provide a theoretical basis for the development of novel therapeutic strategies for DRE.