To evaluate the role of sealants in the prevention of enamel white spot lesions (EWSLs) around bonded orthodontic brackets. Eight databases and grey literature were searched for randomized or quasirandomized controlled clinical trials that assessed the placement of sealants around bonded brackets for the prevention of demineralization during fixed orthodontic treatment. Two reviewers independently selected studies, extracted data, assessed the risk of bias using Cochrane Risk of bias tool 2.0, and evaluated the certainty of evidence using the GRADE approach. Eight clinical trials were included for qualitative synthesis; five of which assessed the outcome at debonding and hence were included for quantitative synthesis. Odds ratios (ORs) were calculated using the corrected Becker-Balagtas method. The OR of EWSLs in the sealants group versus the control group was found to be 0.69 (95 percent confidence interval [95% CI] equals 0.53, 0.89; P=.005) in the five included studies; however, after performing sensitivity analysis by excluding two studies with high risk of bias, the value was 0.68 (95% CI equals 0.41, 1.13; P=0.138). The certainty of evidence regarding the effectiveness of sealants in the prevention of the EWSLs was found to be moderate (downgraded because of the study limitations).