Periodontal pathogens in plaque biofilm initiate periodontitis, which is influenced by genetic and environmental factors. The resultant pro-oxidant status imposed on the periodontium, exacerbated by episodic hyperinflammatory damage contributes to progression of periodontitis and tooth loss in susceptible subjects. Increasing documentation of bi-directional connections between periodontal and cardiometabolic disorders makes it an intriguing area of therapeutic intervention for mutual benefit. Periodontitis and associated comorbidities demonstrate similar risk markers of inflammation during disease progression. Depending on the extent and severity of the inflammatory response, periodontitis could impact significantly on systemic inflammatory loading and influence the progression of endothelial dysfunction, atherosclerotic plaque instability, dyslipidaemia and insulin resistance. Some of the common mechanisms involved are discussed, relevant to periodontal and cardiometabolic disorders which have been documented as having a bidirectional relationship with periodontal disease progression; abating in response to treatment. Periodontal disease may be a useful marker of a susceptible immune system, or directly affect the progression of systemic diseases due to inflammatory loading. These mechanisms mediated by coordinated actions of cytokines, acute phase proteins, enzymes and their sequelae are addressed in the context of conventional periodontal therapy and its outcome with a modulatory role on metabolic diseases. Applications for the role of nutritional and therapeutic antioxidants as adjuncts in diseases with a distinctly prooxidant profile are discussed. Accurate therapeutic targeting as an adjunct to conventional periodontal treatment in this context, for mutual benefit to subjects with periodontitis and cardiometabolic diseases is a challenge.