Post-stroke depression (PSD) is the most common mental complication after stroke, seriously affecting recovery of neurological function and quality of life. Although antidepressants are currently the first-line treatment, they have limitations such as cardiotoxicity, gastrointestinal reactions, and relatively high costs. As a nonpharmaceutical intervention method integrating traditional Chinese medicine and modern neuroanatomy, auricular therapy has shown unique advantages in PSD treatment through a multi-target regulatory mechanism. From the perspective of neurobiology, this article systematically reviews the mechanism of auricular therapy in PSD intervention, including: ( 1 ) the regulation of monoamine and amino acid neurotransmitter homeostasis;(2) promoting neural plasticity and the reorganization of brain network functions; (3) inhibiting neuroinflammation and oxidative stress responses; (4) and regulating the neuroendocrine system. This review aims to comprehensively explain the mechanism by which auricular therapy alleviates PSD through a multidimensional neuro-immune-endocrine regulatory network to promote further research and application in PSD treatment.