Oral cavity that harbors diverse bacterial populations could also act as a site of origin for spread of pathogenic microorganisms to different body sites, particularly in immunocompromised hosts, patients, the elderly, or the underprivileged. A number of recent publications have advocated that patients with periodontal diseases are more susceptible to metabolic endotoxemia, inflammation, obesity, type 2 diabetes, and other related systemic complications, concluding that periodontal diseases could be a potential contributing risk factor for a wide array of clinically important systemic diseases. However, despite a significant increase in the prevalence of periodontal infections and systemic diseases in the past few decades, the fundamental biological mechanisms of connection between these ailments are still not fully explicated. Consequently, the mechanisms by which this bidirectional damage occurs are being explored with a concentric vision to develop strategies that could prevent or control the complications of these ailments. This paper attempts to summarize and hypothesize the diverse mechanisms that hint to a certain connection between the two prevalent chronic situations.