This review aimed to evaluate findings related to the human normal salivary microbiomes, the presence of opportunist salivary microbiome concerning oral and systemic diseases, and the use of salivary microbiome metagenomic analysis. Method: This review accomplishes using PubMed, Science Direct, and Google scholar. After reading the titles and abstracts, 2.718 works of literature screens for this review, content analysis performs. Results: Human normal salivary microbiomes consist of yeast, gram-positive, and gramnegative bacteria. A commensal microbial community founds in healthy people. An opportunist microbial community establishes in unhealthy people. It is essential to note an association between the opportunist microbiome composition with the personal health condition. Specific opportunist microbiome relates to particular diseases, such as diabetes, respiratory diseases, cancer, autoimmune, and viral infections. Even is different results of the conventional method and the modern methods (metagenomic analysis), both approaches can determine the presence of specific opportunist salivary microbiome concerning certain systemic diseases. Conclusion: Salivary microbiome composition can be a biomarker for people's health conditions and various systemic diseases. Both conventional methods and the modern method can be used complementarily for biomarker determination.