This review compares the effects of peripheral dexamethasone and dexmedetomidine on postoperative analgesia. We included six randomized controlled trials (354 patients) through a systematic literature search. We found that analgesia duration was comparable between dexamethasone and dexmedetomidine (58.59 min, 95% CI (confidence interval), −  66.13, 183.31 min) with extreme heterogeneity. Secondary outcome was also compared and no significant difference was observed in sensory block onset and duration and motor block duration and also for postoperative nausea and vomiting. It is noteworthy that dexamethasone reduced analgesic consumption (fentanyl) by 29.12 mcg compared with dexmedetomidine. We performed subgroup analyses and found no significant difference between the following: (1) lidocaine vs ropivacaine (P = 0.28), (2) nerve block vs nerve block + general anesthesia (P = 0.47), and (3) upper limb surgery vs thoracoscopic pneumonectomy (P = 0.27). We applied trial sequential analysis to assess the risks of type I and II errors and concluded that the meta-analysis was insufficiently powered to answer the clinical question, and further analysis is needed to establish which adjuvant is better. In conclusion, we believe that existing research indicates that dexamethasone and dexmedetomidine have equivalent analgesic effects in peripheral nerve blocks.