Abstract: Periodontal pathogens are the main pathogenic factor of periodontitis. Periodontal pathogens have a large variety of virulence factors such as lipopolysaccharide, fimbriae and proteases, which enables the pathogens to infect periodontal tissues and stimulate the secretion of inflammatory cytokines, causing chronic systemic inflammation. Periodontal pathogens may invade multiple systems such as the circulatory system, immune system, respiratory system and digestive system to cause systematic diseases. Recent studies have shown that periodontal pathogens may have close relations with systemic diseases such as cardiovascular disease, diabetes, rheumatoid arthritis, and cancer. Among the periodontal pathogens, Porphyromonas gingivalis can be found in atherosclerotic plaques to impairing the function of the vascular endothelium; Porphyromonas gingivalis may also increase the level of inflammatory factors such as TNF-α to promote insulin resistance and diabetes. Many of the periodontal pathogens such as Porphyromonas gingivalis, Tannerella forsythia and Prevotella intermedia can be detected in the synovial fluid of rheumatoid arthritis patients, suggesting their involvement in the pathogenesis of rheumatoid arthritis. Fusobacterium nucleatum may cause alterations in the intestinal microbiome in mice and promote the occurrence of intestinal tumors. Herein we review the recent progresses in the relationship between periodontal pathogens and systemic diseases.