The oral microbiome is an important part of the human microbiome. The oral cavity has the second largest microbiota after the intestines, and its open structure creates a special environment. With the development of technology such as next-generation sequencing and bioinformatics, extensive in-depth microbiome studies have become possible. They can also be applied in the clinical field in terms of diagnosis and treatment. Many microbiome studies have been performed on oral and systemic diseases, showing a close association between the two. Understanding the oral microbiome and host interaction is expected to provide future directions to explore the functional and metabolic changes in diseases, and to uncover the molecular mechanisms for drug development and treatment that facilitate personalized medicine.