Objective The aim of this systematic review was to evaluate the effectiveness of removable complete denture disinfection using microwaves for the treatment of denture stomatitis. Methods This review identified studies comparing the efficacy of microwave prosthesis disinfection (I) to topical antifungal therapy (C) in the treatment of denture stomatitis (O), which included only individuals who used complete dentures and presented with denture stomatitis (P). The search was performed in six databases and identified 1524 records; after the removal of duplicates, 816 articles remained. Three articles were selected for qualitative synthesis and two for meta‐analysis. Random‐effects meta‐analysis estimated the polled effects of microwave disinfection and antifungal therapy on the Candida counts and clinical manifestation of denture stomatitis. The GRADE approach was used to estimate the certainty of evidence. Results All included studies reported significant reductions in Candida counts and the frequency of denture stomatitis of groups subjected to microwave disinfection of dentures and topical antifungal therapy with nystatin. Significative differences between treatments were only detected for Candida quantification in the palate, within 90 days follow‐up period (SMD = 0.47, 95% CI = 0.02–0.91). Meta‐analyses did not show any further differences between treatments (p > .05), considering the Candida quantification in dentures and the frequency of clinical signs of denture stomatitis. The certainty of the evidence was considered as low, according to GRADE approach. Conclusion Microwave disinfection of complete dentures can be considered as efficient as antifungal therapy for the treatment of denture stomatitis. However, further well‐designed studies are necessary to confirm such evidence.