In the process of orthodontic treatment, the balance between the modeling of alveolar bone and the mechanical stress exerted by the appliance is key to the effective movement of orthodontic teeth. Alveolar bone modeling involves many regulatory factors, and microRNAs (miRNAs), as posttranscriptional regulatory factors, play an important role in the occurrence of bone modeling. As an important member of the miRNA family, miRNA-21 promotes the differentiation of periodontal ligament stem cells into osteoblasts and plays an important role in maintaining bone balance and preventing bone resorption as a regulator of osteoclast formation and a promoter of osteoclast differentiation. A literature review showed that miRNA-21 can regulate osteoclast function and promote bone resorption through programmed cell death 4 (PDCD4), phosphate and tension homology deleted on chromosome ten (PTEN), receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG). MiRNA-21 is highly sensitive to external mechanical stress in the process of orthodontic tooth movement. After orthodontic force is applied, miRNA-21 can promote osteoclast formation and accelerate orthodontic movement; through targeted regulation of periodontal ligament associated protein-1 (PLAP-1), it can regulate periodontal ligament remodeling in the late stage of tooth movement and improve the potential of tooth movement. In addition, miRNA-21 mediates orthodontic tooth movement (OTM) and alveolar bone remodeling in the periodontal inflammatory microenvironment. miRNA-21 can upregulate the expression of hypoxia-inducible factor-1α (HIF-1α) in periodontal ligament stem cells in a hypoxic environment. It can promote the expression of osteogenic markers, such as osteopontin (OPN), osteocalcin (OCN), alkaline phosphatase (ALP) and runt-related transcription factor 2 (Runx2), and promote osteogenic differentiation during orthodontic tooth movement.