The oral cavity is a complex and complete ecosystem. In addition to the microbial community, anatomical structure, temperature, humidity, pH, nutrient sources, proteases, and external factors all influence the ecosystem. Under normal circumstances, this ecosystem maintains a dynamic balance with the host. However, due to the large number of influencing factors, this dynamic balance is fragile. Abnormal changes in a certain factor can disrupt this balance and cause oral cavity disease. Increasing studies have confirmed the role of genetic factors in the etiology of oral diseases. With the understanding of the pathogenesis of oral diseases, the pathogenic factors induced by oral diseases have attracted more attention. This article reviews the key role of epigenetic changes induced by pathogenic factors, such as bacteria, viruses, and cytokines, in the pathogenesis of oral diseases and contributes to the development and application of related drugs.