One‐lung ventilation (OLV), a common ventilation technique, is associated with perioperative lung injury, tightly connected with inflammatory responses. Dexmedetomidine has shown positive anti‐inflammatory effects in lung tissues in pre‐clinical models. This study investigated the efficacy of dexmedetomidine for suppressing inflammatory responses in patients requiring OLV. We searched PubMed, MEDLINE, Embase, Scopus, Ovid, and Cochrane Library for randomized controlled trials focusing on dexmedetomidine’s anti‐inflammatory effects on patients requiring OLV without any limitation on the year of publication or languages. 20 clinical trials were assessed with 870 patients in the dexmedetomidine group and 844 in the control group. Our meta‐analysis investigated the anti‐inflammatory property of dexmedetomidine perioperatively [T1 (30‐min OLV), T2 (90‐min OLV), T3 (end of surgery) and T4 (postoperative day 1)], demonstrating that dexmedetomidine’s intraoperative administration resulted in a significant reduction in serum concentration of interleukin‐6, tumor necrosis factor‐α and other inflammatory cytokines perioperatively. By calculating specific I 2 index, significant heterogeneity was observed on all occasions, with I 2 index ranging from 95% to 99%. For IL‐6 changes, sensitivity analysis showed that the exclusion of a single study led to a significant decrease of heterogeneity (96%–0%; p