Background/Objectives: Periodontitis is a chronic inflammatory disease with marked inter-individual heterogeneity and well-established links to cardiometabolic and other systemic conditions. Conventional clinical diagnostics remain indispensable. However, they provide limited real-time insight into molecular activity and host-response biology. This review aimed to synthesize recent advances in point-of-care diagnostics and emerging molecular biomarkers relevant to periodontal disease and its systemic associations. Methods: We performed a state-of-the-art narrative review of literature published between 2018 and 2026. The focus was on point-of-care biosensing technologies and molecular biomarkers assessed in oral and related biological matrices. These included saliva, gingival crevicular fluid, blood, and dental plaque. Evidence was prioritized based on analytical performance, clinical validity, and translational readiness. Results: Substantial progress has been made in multiplex optical and electrochemical point-of-care platforms. These include microfluidic systems and early intraoral wearable sensors. Such technologies enable quantification of host-response proteins, including MMP-8, cytokines, and chemokines. In parallel, omics-derived biomarkers are emerging as clinically informative adjuncts for diagnosis and monitoring. MicroRNAs, cell-free DNA, extracellular vesicle–derived signals, proteomic profiles, and microbiome classifiers demonstrate promising discrimination. They also provide mechanistic links to systemic inflammation. Clinical translation remains limited by study heterogeneity, spectrum bias, and insufficient external validation. Conclusions: Near-term clinical value lies in adjunctive risk stratification and longitudinal disease monitoring. Replacement of conventional periodontal examination is not currently justified. Meaningful clinical and public-health impact will require standardized disease definitions. Harmonized sampling and reporting protocols are essential. Multicenter validation across comorbidity strata is needed. Regulatory-grade evidence must be generated for in vitro diagnostics and artificial intelligence software classified as medical devices.
Biesiadecki et al. (Mon,) studied this question.