A cumulative review with a systematic approach aimed to provide a comparison of studies’ investigating the possible impact of the active form of vitamin D3, calcitriol (CTL), on the tooth movement caused by orthodontic forces (OTM) by evaluating the quality of evidence, based on collating current data from animal model studies, in vivo cell culture studies, and human clinical trials. Methods: A strict systematic review protocol was applied following the application of the International Prospective Register of Systematic Reviews (PROSPERO). A structured search strategy, including main keywords, was defined during detailed search with the application of electronic database systems: Medline/Pubmed, EMBASE, Scopus, Web of Science, and PsycINFO. In addition, a search was carried out with the use of ClinicalTrials.gov search in order to include ongoing or recently completed trials. The Oxford Level of Evidence and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was utilized to critically evaluate the risk of bias and relative quality of studies included. Meta-analysis with the use of RevMan5 software, random effect, and inverted variable method allowed the quantification of cumulative results. Results: Twenty-seven studies were identified which fulfilled inclusion criteria, including two clinical studies. The assessed level of evidence was variable and inconsistent, predominantly being moderate or low due to a significant difference in study design, sample size, and study protocols. Data synthesis rendered from meta-analysis involving various CTL doses demonstrated slight discrepancies in tooth movement between control and experimental groups (mean difference = 0.27; 95% CI: 0.01–0.53, std mean difference = 0.49; 95% CI: 0.09–0.89), as well as relatively moderate heterogenicity. Conclusions: Although it has been suggested that CTL could accelerate OTM in animal studies and clinical context, these scarce data were supported by a low level of evidence and the studies were carried out using inadequate sample size. Well-powered RCT studies would help to overcome the lack of robustness of the research.
