Orthodontic tooth movement (OTM) is facilitated by the induction of mechanical force, which triggers a sterile inflammatory response in the periodontal tissues. This response, in turn, coordinates the processes of bone resorption and formation. Through an extensive review of the existing literature on the biology of OTM, it becomes evident that macrophages play a pivotal role in all stages of the process. Furthermore, researchers have identified various emerging drugs and biological agents that target the behavior of macrophages, aiming to regulate and control the rate of OTM. To date, most studies have primarily focused on investigating the effects of anti-inflammatory drugs on the rate of OTM and elucidating their specific mechanisms. However, there is a notable absence of reports specifically addressing drugs capable of accelerating tooth movement. Nonetheless, in other fields, such as the promotion of fracture healing, techniques for modulating macrophage function using bio-scaffolds or sustained-release formulations loaded with cytokines or drugs have demonstrated significant advancements. Thus, these techniques hold promise as important avenues for future research and development, exploring the potential of macrophages in regulating the rate of OTM.