Senkyunolides show promise for migraine but face stability challenges requiring further development.

Migraine, ranked as the second most disabling neurological disorder globally, affects over 1 billion people, imposing a substantial worldwide burden. The complexity of its pathological mechanisms contributes to therapeutic limitations. While existing first-line drugs offer partial efficacy, their utility is often constrained by cardiovascular risks, medication-overuse headaches, low bioavailability, and high treatment costs, necessitating novel therapies that balance efficacy and safety. Notably, senkyunolides, core bioactive compounds derived from traditional anti-migraine herbs like Ligusticum chuanxiong, have emerged as promising candidates due to the role of multidimensional homeostasis in regulating neurovascular units (suppressing activation of the trigeminal vascular system, modulating pathological vascular alterations, modulating neurotransmitters and receptors, inhibiting inflammatory response, antioxidant stress and analgesic effects and improving blood-brain barrier integrity) and unique pharmacokinetic advantages (small-molecule structure enabling blood-brain barrier penetration, natural origin reducing hepatorenal toxicity risks). This review systematically analyzes senkyunolides' chemical diversity, extraction methodologies, and anti-migraine pharmacological mechanisms. It further evaluates innovative solutions addressing the critical clinical translation bottleneck of instability. Beyond providing theoretical and technical foundations for developing “multi-target, low-toxicity” anti-migraine drugs, this work deepens understanding of transforming natural products into precision medicines, establishing a new paradigm for efficient and safe therapeutics. Future research must prioritize resolving formulation stability issues and rigorously advancing the clinical translation pipeline.