Purpose This study primarily evaluated the efficacy and safety of prophylactic dexamethasone in preventing radiation-induced pain flare in patients with bone metastases undergoing palliative radiotherapy. Methods A systematic search of the PubMed, Embase, and Cochrane databases was conducted to identify prospective randomized controlled trials published up to May 2026. After screening, six studies were ultimately included. A random-effects model was used for pooled analyses, and sensitivity analyses were performed to assess heterogeneity. Results A total of 1,833 records were initially identified, and six prospective randomized controlled trials were ultimately included in the final analysis. Pooled analysis demonstrated that prophylactic dexamethasone was associated with a significantly lower risk of radiation-induced pain flare compared with placebo (RR = 0.63, 95% CI: 0.46–0.86). Sensitivity analyses did not identify a clear source of heterogeneity within the dexamethasone group. Adverse events were infrequently reported and were generally mild, with no severe treatment-related complications observed in the included studies. Conclusion Prophylactic dexamethasone may reduce the incidence of radiation-induced pain flare in patients with bone metastases undergoing palliative radiotherapy. However, given the limited number of studies and heterogeneity among treatment protocols, these findings should be interpreted cautiously, and further large-scale randomized controlled trials are warranted.