Preservation of the alveolar bone is a determinant in the outcome of orthodontic treatment. Alveolar bone defects or a decrease of their height and width may occur due to common reasons such as inflammation, tooth extraction, or cleft lip and palate. The aim of this systematic review was to investigate and appraise the quality of the most up to date available evidence regarding the applications and effects of platelet-rich fibrin (PRF) in orthodontics. This study was carried out according to preferred reporting items for systematic reviews and meta-analyses guidelines using the following databases: Medline via PubMed, Cochrane Library, Web of Science Core Collection and EMBASE. The qualitative assessment of the included studies was performed using Cochrane Risk of Bias tool and ROBINS-I guidelines. Results: From a total of 489 studies, nine studies were selected. The majority of the included studies demonstrate that autogenous anterior iliac graft with PRF had a higher amount of newly formed bone. Furthermore, this review also suggests that the application of platelet derivatives in the extraction socket can accelerate orthodontic tooth movement. Despite the limitations in the included studies, this systematic review suggested that PRF can improve alveolar cleft reconstruction and orthodontic tooth movement.