Endodontic inflammatory diseases (EIDs), such as pulpitis and apical periodontitis (AP), are common chronic oral inflammatory conditions, which are most commonly caused by untreated dental caries. Over the past two decades, several studies have reported positive bidirectional associations between AP and various systemic conditions, including cardiovascular disease (CVD), diabetes, hepatic disease, inflammatory bowel disease (IBD), hematological disease, and adverse pregnancy outcomes (APOs). These associations indicate that chronic oral inflammation may contribute to systemic low-grade inflammation, potentially influencing overall health. Although current data support strong correlations, no definitive causal relationship has been established to date. Recent studies have suggested that successful endodontic treatment can reduce the level of several systemic inflammatory markers, emphasizing the broader role of oral healthcare in systemic disease prevention. As the field of endodontic medicine continues to evolve, further high-quality longitudinal studies are needed to determine causality and explore the biological mechanisms underlying these associations, highlighting the importance of integrated oral–systemic healthcare.