This review examines the bidirectional relationship between periodontitis and systemic health conditions, offering an integrated perspective based on current evidence. It synthesizes epidemiological data, biological mechanisms, and clinical implications to support collaborative care strategies recognizing oral health as a key component of overall wellness. Periodontitis affects 7.4% to 11.2% of adults worldwide, and its prevalence increases with age. Beyond its local effects, including gingival inflammation, periodontal pocket formation, and alveolar bone loss, periodontitis is associated with various systemic conditions. Emerging evidence has established links with obesity, diabetes mellitus, cardiovascular disease, chronic kidney disease, inflammatory bowel disease, rheumatoid arthritis, respiratory diseases, adverse pregnancy outcomes, certain malignancies, neurodegenerative diseases, psychological disorders, and autoimmune conditions. These associations are mediated by 3 primary mechanisms: dysbiotic oral biofilms, chronic low-grade systemic inflammation, and the dissemination of periodontal pathogens throughout the body. The pathophysiology involves elevated levels of pro-inflammatory cytokines (including interleukin 6, tumor necrosis factor alpha, and C-reactive protein), impaired immune function, oxidative stress, and molecular mimicry. Periodontal pathogens, particularly Porphyromonas gingivalis, are crucial in initiating and sustaining systemic inflammatory responses. Treatment of periodontitis has demonstrated measurable improvements in numerous systemic conditions, emphasizing the clinical significance of these interconnections. Periodontitis should be understood as more than just a localized oral disease; it significantly contributes to the overall systemic inflammatory burden, with implications for general health. An integrated, multidisciplinary approach to prevention, early detection, and comprehensive treatment is vital for optimal patient outcomes. Healthcare providers should acknowledge oral health as an essential element of systemic well-being.