The holistic philosophy of traditional Chinese medicine (TCM) embodied in acupuncture therapy has gained novel insights within the neuroimmune regulatory framework. Its mechanistic framework encompasses 3 pivotal dimensions: 1) Acupuncture stimulation at acupoints transduces mechanical signals into neuroelectrical and biochemical signals, initiating localized immunomodulatory microenvironment remodeling; 2) The autonomic nervous system orchestrates systemic and organ-specific immune homeostasis through vagus nerve-mediated anti-inflammatory effects and sympathetic nerve-mediated bidirectional regulatory dynamics; 3) The enteric nervous system facilitates barrier restoration via neuropeptide-microbiota crosstalk, establishing bidirectional gut-brain axis immune communication. Emerging bioelectronic devices based on somatosensory-autonomic reflex circuits are driving the evolution of acupuncture from empirical practice to precision neuromodulation. Future research should integrate multi-omics profiling and artificial intelligence algorithms to construct a comprehensive “mechanical stimulation – neural coding – immune response” mapping paradigm. This will operationalize TCM’s core principle of “treating the root of disease” into targeted neuromodulation strategies against inflammatory and immune-related disorders through defined neural circuit interventions.