Background. Orthodontic appliances induce significant changes in the oral microbiome, but this shift in microbial composition has not been well established by the available evidence yet. Objectives. To perform a systematic review of existing literature in order to assess the taxonomic microbial changes in orthodontic patients during Fixed Appliance Treatment (FAT) and Clear Aligner Treatment (CAT), using next-generation sequencing (NGS) technique of the bacterial 16S rRNA gene. Search Methods and Selection Criteria. The search for articles was carried out in PubMed, including articles published in English until May 2021. They included every human study report potentially relevant to the review. Data Collection and Analysis. After duplicate study selection and data extraction procedures according to the PICOS scheme, the methodological quality of the included papers was assessed by the Swedish Council on Technology Assessment in Health Care Criteria for Grading Assessed Studies (SBU) method. Results. The initial search identified 393 articles, 74 of which were selected by title and abstract. After full-text reading, six articles were selected according to inclusion criteria. The evidence quality for all the studies was moderate. Conclusions. Orthodontic treatment seems to transiently affect the composition of subgingival microbiome, although not salivary, maintaining a stable microbial diversity. Different results were found in the shift of microbiome between plaque and saliva, depending on the type of orthodontic treatment. This review should be interpreted with some caution because of the number, quality, and heterogeneity of the included studies.