This systematic review explores the interaction between cytokines and orthodontic treatment (OT). Cytokines, low-molecular-weight proteins involved in immune responses, play a crucial role in inflammation, bone and soft tissue metabolism, and tissue remodeling during OT. The review highlights the complex relationship between cytokines and OT, emphasizing their diverse properties and mechanisms of action, including autocrine, paracrine, and endocrine activities. OT induces tension and compression in the periodontal ligament (PDL), triggering cytokine release, which influences bone remodeling and tissue responses. Proinflammatory cytokines, such as IL-1β, IL-6, and TNF-α, are elevated in gingival crevicular fluid (GCF) after orthodontic force application, while anti-inflammatory cytokines like IL-4 and IL-10 are involved in healing processes. The choice of orthodontic devices, such as self-ligating brackets, affects cytokine concentrations, indicating the importance of attachment design. Studies show that cytokine levels vary depending on the type of orthodontic treatment, with differences observed between self-ligating and conventional brackets. The review also discusses the impact of chronic diseases, such as type 2 diabetes, on cytokine responses and periodontal health. Additionally, the role of cytokines in orthodontic tooth movement, bone resorption, and the influence of sex and hormone levels on inflammatory responses are highlighted. The findings suggest that understanding cytokine interactions can improve orthodontic practices, optimize patient care, and enhance treatment outcomes. The review underscores the importance of personalized treatment approaches, considering individual biological variations and the need for further research to refine therapeutic strategies.This systematic review explores the interaction between cytokines and orthodontic treatment (OT). Cytokines, low-molecular-weight proteins involved in immune responses, play a crucial role in inflammation, bone and soft tissue metabolism, and tissue remodeling during OT. The review highlights the complex relationship between cytokines and OT, emphasizing their diverse properties and mechanisms of action, including autocrine, paracrine, and endocrine activities. OT induces tension and compression in the periodontal ligament (PDL), triggering cytokine release, which influences bone remodeling and tissue responses. Proinflammatory cytokines, such as IL-1β, IL-6, and TNF-α, are elevated in gingival crevicular fluid (GCF) after orthodontic force application, while anti-inflammatory cytokines like IL-4 and IL-10 are involved in healing processes. The choice of orthodontic devices, such as self-ligating brackets, affects cytokine concentrations, indicating the importance of attachment design. Studies show that cytokine levels vary depending on the type of orthodontic treatment, with differences observed between self-ligating and conventional brackets. The review also discusses the impact of chronic diseases, such as type 2 diabetes, on cytokine responses and periodontal health. Additionally, the role of cytokines in orthodontic tooth movement, bone resorption, and the influence of sex and hormone levels on inflammatory responses are highlighted. The findings suggest that understanding cytokine interactions can improve orthodontic practices, optimize patient care, and enhance treatment outcomes. The review underscores the importance of personalized treatment approaches, considering individual biological variations and the need for further research to refine therapeutic strategies.