Background <p>Chronic pain patients often experience moderate to severe anxiety and depressive symptoms. Growing evidence supporting dexmedetomidine as a potential treatment for mental health conditions, research on its application in chronic pain patients with comorbid anxiety and depression remains limited.</p> Methods <p>Patients who received intravenous infusions of dexmedetomidine during their interventional pain management procedures from January to July 2024 were compared to those who underwent similar procedures without dexmedetomidine infusion during the same period, utilizing propensity score matching.</p> Results <p>A total of 290 patients were included in the analysis from January to July 2024. Propensity score matching resulted in 92 matched pairs for further analysis. At the one-month follow-up, the perioperative application of dexmedetomidine was associated with a greater improvement in anxiety and depression disorders, as measured by the Generalized Anxiety Disorder 7-item scale, showing a reduction of -4.43 points (95% CI, -4.98 to -3.88) compared to -2.42 points (95% CI, -2.97 to -1.87) for the local analgesia group and the Patient Health Questionnaire-9 scores indicated a reduction of -6.19 points (95% CI, -6.84 to -5.55) for the dexmedetomidine group versus -3.92 points (95% CI, -4.56 to -3.28) for the local analgesia group. The use of dexmedetomidine was also associated with a greater improvement of pain(-3.32 points vsurs -2.62 points).</p> Conclusions <p>Intraoperative dexmedetomidine significantly improves anxiety and depression in patients with chronic pain. Therefore, dexmedetomidine may serve as a promising adjunctive treatment for chronic pain patients, particularly those with comorbid anxiety and depression.</p> Clinical trial number <p>Not applicable.</p>