Background <p>Migraine is a chronic neurological disorder characterized by severe headache, nausea, and sensitivity to light and sound, affecting approximately 1 billion people globally. Despite advances in understanding migraine pathophysiology, particularly with the emergence of CGRP-targeted therapies, the mechanisms underlying neuroinflammation and glial contributions remain poorly understood. Current treatments are effective for a subset of patients, yet they don’t tackle the fundamental neurogenic and neuroinflammatory processes that fuel chronic migraine, especially the pathophysiological aspects contributed by glial cells.</p> Principal findings <p>This review integrates recent preclinical and clinical evidence to elucidate how diverse glial cells, including central glia (astrocytes, microglia and oligodendrocytes) and peripheral glia (Schwann cells, satellite glial cells), coordinate the neuroinflammation associated with migraine. Evidence shows that astrocytes and microglia are essential to both cortical spreading depolarization (CSD) and mediating the inflammatory cascades that maintain chronic pain. Oligodendrocytes, though less studied, are predicted to affect neuronal excitability and energy metabolism, while Schwann cells and satellite glial cells mediate peripheral nociceptive signaling through their interactions with neural and immune elements. New therapeutic strategies have been put forward. These include targeting glial-specific signaling pathways and employing advanced drug delivery systems such as viral vectors and nanoparticles to improve treatment effectiveness.</p> Conclusion <p>Glial cells are pivotal regulators of migraine-associated neuroinflammation. This review underscores their critical role in migraine pathophysiology and highlights glial-targeted therapies as a promising direction for future research and treatment development.</p>