Abstract: Post-stroke depression (PSD) is a common post-stroke complication with limited treatment options and significant adverse effects from conventional drugs. Acupuncture, a multi-target holistic non-pharmacological intervention, shows unique clinical advantages. This review provides the first systematic synthesis of the central neurobiological mechanisms underlying acupuncture’s therapeutic effects on PSD. The identified mechanisms include promoting neuroplasticity via the BDNF/TrkB pathway and rebalancing neurotransmitter systems (monoamines and glutamate/GABA). Additionally, acupuncture inhibits microglial activation and TLR4/NF-κB/NLRP3-driven neuroinflammation, restores mitochondrial homeostasis through AMPK-dependent autophagy, and modulates the gut microbiota–brain axis. Together, these findings elucidate the “multi-target, network-based” characteristics of acupuncture from a modern scientific perspective, providing a scientific basis for traditional Chinese acupuncture principles. By integrating recent mechanistic advances, this review addresses literature gaps and offers a theoretical foundation for optimizing clinical strategies, promoting mechanism-driven personalized interventions, and bridging traditional Chinese medicine with contemporary neuroscience. Keywords: post-stroke depression, acupuncture, electroacupuncture, neurobiology, mitochondrial function, gut–brain axis
Cao et al. (2026) studied this question.