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One‐third of epilepsy patients have drug‐resistant epilepsy (DRE), which is often complicated by polydrug toxicity and psychiatric and cognitive comorbidities. Advances in understanding the microbiome and gut‐brain‐axis are likely to shed light on epilepsy pathogenesis, anti‐seizure medication (ASM) resistance, and potential therapeutic targets. Gut dysbiosis is associated with inflammation, blood‐brain barrier disruption, and altered neuromodulators. High‐throughput and metagenomic sequencing has advanced the characterization of microbial species and functional pathways. DRE patients show altered gut microbiome composition compared to drug‐sensitive patients and healthy controls. The ketogenic and modified Atkins diets can reduce seizures in some patients with DRE. These low‐carbohydrate dietary therapies alter the taxonomic and functional composition of the gut microbiome, and composition …