Periodontitis is a biofilm-driven inflammatory disease in which conventional indices (probing depth, clinical attachment level, and radiographs) quantify tissue destruction without capturing the biology of infection. In this review, we synthesized microbiological diagnostics, from chairside tools to omics. We outline sampling strategies and emphasize the quantitative monitoring of bacterial load. Enzymatic assays (e.g., N-benzoyl-DL-arginine-2-naphthylamide hydrolysis assay test) measure functional activity at the point of care. Immunological methods include rapid immunochromatography for Porphyromonas gingivalis and enzyme-linked immunosorbent assay for the high-throughput measurement of bacterial antigens. Molecular platforms encompass quantitative polymerase chain reaction (qPCR) (TaqMan, SYBR, multiplex panels; propidium monoazide quantitative-qPCR for viable cells), checkerboard DNA–DNA hybridization for semi-quantitative community profiling, loop-mediated isothermal amplification (LAMP)/molecular beacon-LAMP for portable isothermal detection, and microarrays. Complementary modalities such as fluorescent in situ hybridization, next-generation sequencing, and Fourier transform infrared spectroscopy provide spatial, ecological, and biochemical resolutions. We discuss the limitations of current approaches, including sampling bias, presence–activity discordance, semi-quantitation, method biases, limited strain/function resolution, low-biomass artifacts, and lack of validated cutoffs. To address these challenges, we propose a pragmatic hybrid strategy: site-specific quantitative panels combined with activity and host-response markers interpreted alongside clinical metrics under standardized quality assurance/quality control. Priorities include outcome-linked thresholds, strain-aware/functional panels, robust point-of-care chemistry, and harmonized protocols to enable personalized periodontal care.

Trypsin-like peptidase (TLP) activity has emerged as a promising chairside biomarker for periodontal disease, but its relationship with local inflammatory biomarkers has not been fully elucidated. This study aimed to compare the associations of TLP activity and gingival crevicular fluid (GCF) C-reactive protein (CRP) concentration with local periodontal conditions. Sixty patients with untreated periodontitis were enrolled, and GCF and subgingival plaque samples were collected from the deepest periodontal pocket of each participant. TLP activity was measured using a chairside assay, GCF CRP concentration by enzyme-linked immunosorbent assay, and Porphyromonas gingivalis (P. gingivalis), Treponema denticola, and Tannerella forsythia by real-time PCR. GCF CRP concentration was not associated with clinical periodontal parameters or microbiological findings, whereas TLP activity was significantly associated with probing pocket depth and P. gingivalis counts. In multivariable analysis including age, probing pocket depth, bleeding on probing, GCF CRP concentration, and P. gingivalis counts, age, probing pocket depth, and P. gingivalis counts were independently associated with TLP activity. These findings suggest that TLP activity better reflects local clinical and microbiological periodontal conditions than GCF CRP concentration and may provide complementary information to conventional periodontal assessment.