Nowadays, there is a considerable interest to study the biological and microbiological changes that accompany orthodontic treatment. Growing knowledge on oral microbiota allows, day after day, to identify and characterize the microbial arrangements specifically associated with oral and extra-oral conditions. The aim of the present work is to highlight any further correlations between orthodontic appliances and the qualitative and quantitative modifications of the oral microbiota, such as predisposing factors for the onset of caries, periodontal diseases, and other infections, which can impact the oral and systemic health of the orthodontic patients. When compared with subjects without orthodontic appliances, orthodontic patients reported significant qualitative and quantitative differences in supra- and subgingival plaque during the entire treatment period. Certain components of fixed appliances (mainly bonded molar brackets, ceramic brackets, and elastomeric ligatures) showed high risks of periodontal disease and tooth decay for patients. An unclear prevalence of Candida spp. and the paucity of studies on viruses and protozoas in the oral microbiota of orthodontic patients need to be further investigated. The evidence emerging from this study could guide clinicians in modulating the timing of controls and enhance patient motivation to prevent the formation of mature plaque, thus reducing the risks of oral-plaque-related diseases.