Objectives <p>Apical periodontitis (AP) is an inflammatory immune response in periapical tissues caused by microbial infections. Failure of root canal treatment or delayed healing is often due to intracanal or extra-radicular bacteria. However, beyond microbial factors, the patient’s systemic health can significantly influence the progression and healing of AP. Metabolic syndrome is a risk factor and it is characterized by a cluster of interconnected metabolic risk factors, including abdominal obesity, hyperlipidemia, hypertension, and hyperglycemia.</p> Materials and methods <p>A comprehensive literature review was conducted on apical periodontitis and metabolic syndrome, and their impact on the roles of different immune cell populations.</p> Results <p>Both AP and metabolic syndrome are inflammatory diseases that involve complex and interwoven immune responses. The affected immune cells are categorized into the innate (neutrophils, macrophages, and dendritic cells) and adaptive immune systems (T cells and B cells).</p> Conclusions <p>Metabolic diseases and AP are closely correlated, possibly intertwined in a two-way relationship driven by a shared dysregulated immune response.</p> Clinical relevance <p>Understanding the pathophysiology and immune mechanisms underlying the two-way relationship between metabolic syndrome and AP can help improve treatment outcomes and enhance the overall well-being of patients with endodontic disease complicated by metabolic syndrome.</p>