Abstract <p>Epilepsy, a neurological disorder characterized by recurrent seizures, presents significant therapeutic challenges, with roughly 30% of individuals demonstrating resistance to antiepileptic drugs. Drug-resistant epilepsy diminishes patients’ quality of life and underscores the critical need for innovative therapeutic approaches. MicroRNAs, small non-coding RNA molecules, have emerged as key regulators in the pathogenesis of epilepsy, influencing neuronal excitability, synaptic plasticity, and neuroinflammatory processes. By targeting multiple genes and pathways involved in epileptogenesis, miRNAs offer promising opportunities for precision medicine. This review explores the dual roles of specific miRNAs in epilepsy, acting as both promoters and inhibitors of pathogenic pathways, and highlights recent advancements in miRNA-based therapeutic delivery systems. State-of-the-art approaches, including lipid nanoparticles, viral vectors, and exosome-based systems, are being developed to address challenges such as blood–brain barrier penetration, targeted delivery, and minimizing systemic side effects. These advancements lay the groundwork for more effective and personalized treatment strategies.</p> Graphical Abstract <p></p>