Post-stroke depression (PSD) is a common neuropsychiatric complication following stroke and has emerged as a major public health concern due to its adverse impact on post-stroke prognosis. Clinical studies have confirmed that early intervention with electroacupuncture can significantly reduce PSD incidence and alleviate depressive severity. Mechanistically, electroacupuncture exerts antidepressant effects through inhibition of the endoplasmic reticulum stress pathway and attenuation of neuronal apoptosis. Dexmedetomidine, a highly selective α₂-adrenergic receptor agonist, not only provides sedation and analgesia but also confers neuroprotective actions, including anti-inflammatory, anti-apoptotic, and blood-brain barrier protective effects. Its efficacy in preventing postpartum depression has been clinically validated. Given the substantial burden of PSD and the limitations of existing preventive approaches, the present study aims to investigate the value of a combined electroacupuncture and dexmedetomidine strategy for PSD prevention, with the goal of developing a safe and effective integrative treatment regimen for this frequent post-stroke complication.