BACKGROUND Little is known about the extent to which hydrogen peroxide as used for tooth bleaching could be carcinogenic to the oral mucosa. OBJECTIVE The purpose of this systematic review and meta-analysis was to evaluate whether hydrogen peroxide as used for tooth bleaching has carcinogenic effects on the oral mucosa. METHODS PubMed, Web of Science, Scopus, and Embase electronic databases were searched. Studies evaluating different outcomes potentially related to the carcinogenic effects of hydrogen peroxide for tooth bleaching on the oral mucosa were included. Risk of bias was assessed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE), Risk Of Bias in Non-randomized Studies of Interventions (ROBINS-I), or Risk of Bias 2 (RoB 2) tools. The strength of the evidence was assessed by using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. The quantitative analysis was performed with means, standard deviations, and 95% confidence intervals (CIs). Heterogeneity was analyzed by using I-squared statistics. RESULTS Thirteen articles comprising 5 animal and 8 clinical studies met the inclusion criteria. Three of the 5 animal studies associated the bleaching agents with a carcinogen and demonstrated an enhancement of the carcinogenic effect, but probably with the bleaching agent acting only as a promoter. Five clinical studies concluded that the bleaching agents did not cause mutagenic stress on the oral mucosa by using the micronucleus test. The meta-analysis demonstrated that the frequency of micronuclei did not differ significantly between baseline and 30 days after bleaching (mean difference: 0.48; 95% CI, -1.49, 2.46; P=.63). CONCLUSIONS This systematic review indicated that hydrogen peroxide does not appear to have carcinogenic effects on the oral mucosa.