Aging is associated with the development of disease. Periodontal disease is one of the many diseases and conditions that increase in prevalence with age. In addition to the traditional focus on individual age-related conditions, there is now a greater recognition that multisystem conditions such as frailty play an important role in the health of older populations. Frailty is a clinical condition in older adults that increases the risk of adverse health outcomes. Both frailty and periodontal disease are common chronic conditions in older populations and share several risk factors. There is likely a bidirectional relationship between periodontal disease and frailty. Comorbid systemic diseases, poor physical functioning, and limited ability to self-care in frail older people have been implicated as underlying the association between frailty and periodontal disease. In addition, both frailty and periodontal disease also have strong associations with inflammatory dysregulation and other age-related pathophysiologic changes that may similarly underlie their development and progression. Investigating age-related changes in immune cells that regulate inflammation may lead to a better understanding of age-related disease and could lead to therapeutic targets for the improved management of frailty and periodontal disease.