The oral cavity has a specific microenvironment, and structures such as teeth are constantly exposed to chemical and biological factors. Although the structure of the teeth is permanent, due to exposure of the pulp and root canal system, trauma can have severe consequences and cause the development of local inflammation caused by external and opportunistic pathogens. Long-term inflammation can affect not only the local pulp and periodontal tissues but also the functioning of the immune system, which can trigger a systemic reaction. This literature review presents the current knowledge on root canal infections and their impact on the oral microenvironment in the context of immune system disorders in selected diseases. The result of the analysis of the literature is the statement that periodontal-disease-caused inflammation in the oral cavity may affect the development and progression of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, or Sjogren’s syndrome, as well as affecting the faster progression of conditions in which inflammation occurs such as, among others, chronic kidney disease or inflammatory bowel disease.