Orthodontic tooth movement (OTM) involves the application of mechanical forces, leading to bone remodeling through a coordinated immune response. This process comprises four stages—initial, lag, acceleration, and retention—each characterized by specific immune mechanisms involving cytokines, immune cells, and signaling pathways. Inflammatory mediators, such as interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α), initiate bone resorption, while regulatory cytokines like IL-10 promote tissue repair. The nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) balance regulates osteoclast activity, ensuring controlled bone remodeling. Understanding these immune responses provides valuable insights into optimizing orthodontic treatment outcomes by controlling inflammation and enhancing therapeutic efficiency. This knowledge is significant for alleviating pain during orthodontic treatment, reducing excessive resorption of periodontal tissues, and preventing post-treatment relapse.