Inflammation in the oral cavity is linked with the occurrence of cardiovascular diseases and hypertension. One of proposed mechanisms involve chronic activation of the immune response induced by local oral inflammatory disorders, which include denture-related stomatitis (DRS). This study aimed to verify links between DRS and changes in the cardiovascular system and peripheral immune response. 44 patients (20 with DRS and 24 from healthy oral mucosa) were recruited. Patients were elderly and the majority of both groups were women. DRS patients were treated with nystatin and examined also immediately and two months after treatment completion (n = 17). DRS patients showed significantly worse endothelial dysfunction as compared to the control group and DRS treatment improve vascular function. There were no changes in blood pressure and intima-media thickness, as well as in the presence of atherosclerotic lesions. The immunological studies showed no unambiguous influence of DRS presence and treatment on primary immune cell populations and their activation. The current study is preliminary and need confirmation, however, due to the high DRS incidence, findings described above have the potential to be of clinical relevance, indicating denture wearers as a group with increased cardiovascular risk.