Hand‐foot syndrome (HFS) is the most common adverse effect of capecitabine‐containing chemotherapy. The purpose of this study was to assess the efficacies of various prevention and treatment strategies for capecitabine‐induced HFS. Searches of the PubMed and Embase databases were performed to identify relevant studies. The risk ratio (RR) with the corresponding 95% confidence interval (CI) was used as an effect measure to evaluate the efficacies of these prevention and treatment strategies. Publication bias was evaluated using Begg's and Egger's tests. Overall and subgroup analyses were conducted. All statistical analyses were conducted with Stata software version 12.0. Seventeen eligible studies were included. Our results indicated that celecoxib was significantly associated with a lower incidence of grade ≥2 capecitabine‐induced HFS without heterogeneity (RR = 0.43, 95% CI = 0.23–0.81, I2 = 0.0%). However, pyridoxine and topical urea/lactic acid were not effective toward preventing capecitabine‐induced grade 1, 2, 3, ≥1 or ≥2 HFS. Moreover, pyridoxine was not effective in treating capecitabine‐induced HFS. Similar results were obtained by subgroup analysis. Our results indicate that celecoxib has potential prophylactic efficacy for capecitabine‐induced HFS. However, pyridoxine and topical urea/lactic acid are not associated with a decrease in the incidence of capecitabine‐induced HFS. What's new? Capecitabine is effective against breast, colorectal and gastric cancers and can be orally administered, making it an appealing therapeutic option. Its use, however, can be limited by the development of hand‐foot syndrome (HFS), a common side effect that negatively impacts quality of life. The effectiveness of HFS prevention strategies is unclear. The authors of this study evaluated previously reported prevention and treatment strategies for capecitabine‐induced HFS. Celecoxib was associated with reduced occurrence of grade 2 or higher HFS, while pyridoxine did not significantly improve HFS symptoms and topical urea/lactic acid was found to be ineffective in preventing the condition.