BackgroundMalocclusion is a common oral disorder. Childhood is a critical period for the development of malocclusion. This protocol will explore the clinical efficacy and safety of bracketless invisible orthosis (BIO) in the treatment of children with malocclusion.MethodsThis study will search MEDLINE, PUBMED, Cochrane Library, Web of Science, WANGFANG, VIP, CNKI, and CBM from inception to the present. We will not apply any limitations to the language and publication status. All potential randomized controlled trials (RCTs) on the efficacy of BIO for the treatment of children with malocclusion will be considered for inclusion. Two authors will independently carry out study identification, data extraction, and study quality assessment in each study. Any disagreement will be resolved through discussion with a third author. When a number of included studies are sufficient, we will conduct meta-analysis, as well as subgroup analysis and sensitivity analysis. The certainty of evidence will be appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Outcome of interest will be presented in summary of findings tables, and statistical analysis will be performed utilizing RevMan 5.4 software. DiscussionThis systematic study will summarize all available studies to investigate the clinical efficacy of BIO in treating children with malocclusion. Findings of this study will highlight efficacy and safety of BIO for the treatment of children with malocclusion for both clinical practice and future strategies. Study registrationOSF (https://osf.io/avpmx).