Human oral microbiota is the ecological community of commensal, symbiotic, and pathogenic microorganisms found in the oral cavity. Oral microbiota generally exists in the form of a biofilm and plays a crucial role in maintaining oral homeostasis, protecting the oral cavity and preventing disease development. Human oral microbiota has recently become a new focus research for promoting the progress of disease diagnosis, assisting disease treatment, and developing personalised medicines. In this review, the scientific evidence supporting the association that endogenous and exogenous factors (diet, smoking, drinking, socioeconomic status, antibiotics use and pregnancy) modulate oral microbiota. It provides insights into the mechanistic role in which oral microbiota may influence systemic diseases, and summarises the challenges of clinical diagnosis and treatment based on the microbial community information. It provides information for noninvasive diagnosis and helps develop a new paradigm of personalised medicine. All these benefit human health in the post-metagenomics era.