This study systematically investigates the clinical efficacy of traditional Chinese medicine (TCM) syndrome differentiation intervention for migraine and its neuroendocrine regulatory mechanism, aiming to provide evidence-based medical support for optimizing clinical diagnosis and treatment strategies for this disease. A total of 120 migraine subjects meeting the inclusion criteria were randomly assigned in a 1:1 ratio to the experimental group and the control group (60 cases each). The experimental group received individualized TCM compound prescription combined with filiform needle acupuncture based on four types identified by four diagnostic methods: hyperactivity of liver Yang, deficiency of both Qi and blood, internal obstruction of phlegm-turbidity, and obstruction of collaterals by blood stasis. The control group was treated with oral flunarizine hydrochloride capsules. The intervention period was 12 weeks, and follow-up observations were extended to the end of the 9th month, with dynamic collection of efficacy endpoints and safety indicators in both groups. Efficacy data showed that the total effective rate of the TCM intervention group was 91.67%, which was significantly higher than 76.67% of the control group, with a statistically significant difference (p < 0.05). At 3 and 6 months of treatment, the TCM treatment group exhibited more significant improvements in Numerical Rating Scale (NRS) scores, migraine attack frequency, and single attack duration; the increase in serum 5-hydroxytryptamine (5-HT) level and the decrease in calcitonin gene-related peptide (CGRP) level were also significantly superior to those in the control group (p < 0.05). The study concludes that TCM treatment based on syndrome differentiation for migraine has definite and reliable clinical efficacy, which can effectively relieve clinical symptoms and reduce attack frequency. Its mechanism of action may be related to regulating 5-HT/CGRP balance, improving vascular function, and inhibiting neurogenic inflammation. This treatment regimen has good clinical safety with no obvious adverse reactions and possesses practical value for extensive promotion.