Objectives. To evaluate the effectiveness of rapid palatal expansion in the treatment of nocturnal enuresis among 6–18-year-old children and adolescents. Methods. Comprehensive searches were carried out in 6 electronic databases (EBSCO, ProQuest, Clinical Key, Science Direct, SCOPUS, and OVID) and supplemented by additional manual searches in 4 orthodontic journals until June 2020. Randomized controlled clinical trials (RCTs) and controlled clinical trials (CCTs) of children and adolescents aged 6–18 years old of both genders who underwent rapid palatal expansion and were considered unresponsive to previous conventional nocturnal enuresis treatment were included in this review. Risk of bias of individual trials was assessed using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) assessment tool for CCTs and the revised Cochrane Risk-of-Bias tool for RCTs (RoB 2). Results. Four studies met all inclusion criteria and were finally included in this systematic review, of which one was an RCT and three were CCTs. Reduction in nocturnal enuresis frequency was reported in all included studies with varying rates and methods of reporting, but most studies reported a statistically significant reduction in the number of wet nights per week. The average range of becoming completely dry 1 year after treatment with an RME was 0%–60%. Also, there was a statistically significant correlation between an improvement in bedwetting and an increase in nasal volume after the use of RME. Conclusion. A rapid palatal expansion device may be considered as an alternative treatment option of the nocturnal enuresis condition with guarded prognosis when other treatment modalities have failed.