Background <p>Despite numerous studies of the anxiolytic effects of dexmedetomidine compared with those of other drugs or saline, the results have been inconsistent. Here we report a systematic review and meta-analysis to comprehensively evaluate the evidence of the anxiolytic effects of dexmedetomidine.</p> Methods <p>This research has been registered in the International Prospective Register of Systematic Reviews. The PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov database were searched for clinical trials that compared the anxiolytic effects of dexmedetomidine with those of a control group with valid anxiety scores from inception to December 29, 2024.</p> Results <p>Overall, this systematic review and meta-analysis included 25 clinical studies with 2159 participants who underwent surgery. The primary outcome revealed that patients who were treated with dexmedetomidine had significantly lower anxiety scores than others did overall (MD = − 1.73, 95% CI = [ − 2.33, − 1.13], <i>p</i> &lt; 0.00001, <i>I</i>^<i>2</i> = 86.5%). Dexmedetomidine was found to be more effective than benzodiazepines in relieving anxiety (MD = − 1.34, 95% CI = [ − 2.08, − 0.60],<i> p</i> = 0.0004,<i> I</i>^<i>2</i> = 83.3%). The secondary outcomes revealed no significant differences in satisfaction, pain level, sedation scores or the risk of postoperative nausea and vomiting between patients who were treated with dexmedetomidine and controls. However, the occurrence of bradycardia was more common in the dexmedetomidine groups.</p> Conclusions <p>Overall, this meta-analysis provided evidence of the potential of dexmedetomidine for relieving anxiety among patients who undergo surgery, with superior antianxiety effects compared with those of benzodiazepines.</p>