Dysbiosis of the oral microbiome has been implicated in the onset and progression of periodontal diseases. An altered oral microbiome can significantly affect the concentration and composition ratio of bacterial-derived metabolites, thereby contributing to disease development. However, there is limited research on the role of metabolites derived from the oral microbiota. This study aimed to identify specific bacteria-derived metabolites and their contributions to pathogenicity. Mouth-rinsed water was collected from 24 patients with periodontal disease and 22 healthy individuals. We conducted a correlation analysis between periodontal disease-associated bacteria and metabolites present in mouth-rinsed water. We evaluated the effects of these metabolites on human gingival epithelial cells analysis of oral bacteria culture supernatants confirmed the origin of these metabolites. We identified 20 metabolites associated with bacteria that are significantly more prevalent in periodontal disease. Notably, propionate, succinate, citrulline, and homoserine-metabolites derived from the oral microbiome-were identified as being associated with periodontal disease. These results suggested that metabolites derived from the oral microbiota are involved in periodontal disease.