ABSTRACT Apical periodontitis is a common oral inflammatory disease that develops as a result of infection of the dental pulp and progresses with destruction of periapical bone. Although generally considered a localized infection, microorganisms in periapical tissues, their toxic by- products, and inflammatory mediators produced at the lesion site may enter systemic circulation. These factors can modulate the host immune response and contribute to the pathogenesis of systemic diseases. Therefore, apical periodontitis should not be regarded solely as a localized dental condition but also as a disease with systemic implications. Conversely, the hyperinflammatory state observed in chronic systemic diseases may influence the progression of apical periodontitis and affect treatment outcomes. However, the nature of this relationship and underlying biological mechanisms have not yet been fully elucidated. In this review, a literature search was conducted using PubMed, Scopus, and Web of Science databases. Keywords including “apical periodontitis,” “systemic diseases,” “inflammation,” “cardiovascular diseases,” “diabetes,” “autoimmune diseases,” and “psychiatric disorders” were used in combinations. Retrieved studies were evaluated based on recency, scientific quality, and relevance, with priority given to recent publications. A better understanding of the interaction between apical periodontitis, systemic inflammation, and chronic diseases may contribute to improved risk management and prognostic outcomes.Accordingly, this review aims to evaluate associations between apical periodontitis and systemic diseases, as well as mechanisms underlying this interaction.