Background: Oral diseases are traditionally diagnosed and monitored using clinical assessment supported by dental imaging. Imaging primarily reflects structural change and may lag behind early inflammatory or metabolic activity. Laboratory biomarkers from saliva, gingival crevicular fluid, and blood have been proposed to complement imaging, potentially improving early detection, risk stratification, and treatment monitoring. Objective: To evaluate the data on integrated use of laboratory biomarkers and dental imaging for diagnosing and monitoring major oral diseases. Methods: We systematically searched open access databases with emphasis on PubMed Central and Scopus, for original human studies assessing at least one laboratory biomarker alongside dental imaging outcomes. Studies addressing periodontitis, peri implant conditions, and apical periodontitis were prioritized. Two reviewers independently screened titles, abstracts, assessed full texts, and extracted study characteristics and key findings. Risk of bias was evaluated using appropriate tools for observational and clinical studies. Results: Eight eligible studies were included. In periodontitis, salivary inflammatory and bone turnover markers (IL 1β, IL 6, MMP 8, ICTP, HGF, osteonectin) were associated with radiographic alveolar bone loss and improved discrimination in disease states when used in panels. Studies in implant dentistry suggested that serum vitamin D status may relate to marginal, crestal bone levels assessed radiographically or by CBCT. In apical periodontitis, systemic inflammatory markers appeared to vary with baseline radiolucency size and treatment response. Conclusion: Available data supports a complementary role for biomarkers with imaging, but heterogeneity and limited longitudinal data prevent firm clinical thresholds.