Periodontal diseases are among the most prevalent chronic inflammatory disorders affecting the oral cavity and are major causes of tooth loss worldwide. The development and progression of periodontal diseases are strongly associated with complex interactions between microbial communities and host immune responses. Advances in next-generation sequencing (NGS), metagenomics, metatranscriptomics, and bioinformatics have transformed the understanding of the oral microbiome and its role in periodontal pathogenesis. Microbiome analysis has revealed that periodontal disease is not caused by a single pathogen but results from dysbiosis within polymicrobial biofilms. This review comprehensively examines the oral microbiome, methodologies used for microbiome analysis, microbial signatures associated with periodontal diseases, host-microbe interactions, diagnostic applications, therapeutic implications, and future directions. Current evidence highlights the importance of microbiome profiling for early diagnosis, risk assessment, personalized treatment planning, and monitoring therapeutic outcomes. Emerging technologies including artificial intelligence, multi-omics approaches, and precision microbiome-based therapies are expected to revolutionize periodontal disease management.