Periodontal diseases are chronic inflammatory conditions affecting the supporting structures of teeth and remain a major cause of tooth loss worldwide. Traditional diagnostic methods, including probing depth, clinical attachment loss, bleeding on probing, and radiographic assessment, primarily evaluate historical tissue destruction rather than current disease activity. Biomarkers have emerged as valuable tools for the early detection, diagnosis, monitoring, and prognosis of periodontal diseases. These biological indicators, detected in saliva, gingival crevicular fluid (GCF), blood, and tissue samples, provide insights into inflammatory activity, tissue breakdown, bone metabolism, and host immune responses. Recent advances in molecular biology, genomics, proteomics, metabolomics, and artificial intelligence have accelerated the development of biomarker-based diagnostic approaches. This review explores the role of biomarkers in periodontal diagnosis, their biological significance, clinical applications, advantages, limitations, and future directions. Evidence suggests that biomarker-based diagnostics can significantly enhance precision periodontology, facilitate personalized treatment strategies, and improve long-term periodontal outcomes.