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The self-maintenance of the inflammatory process can cause periodontal damage from the alveolar bone resorption to tooth loss in order to contrast the effects of periodontitis, the main therapy used is scaling and root planing (SRP). At the same time, studying the physiopathology of periodontitis has shown the possibility of using a local drug delivery system as an adjunctive therapy. Using local drug delivery devices in conjunction with SRP therapy for periodontitis is a potential tool since it increases drug efficacy and minimizes negative effects by managing drug release. This review emphasized how the use of local drug delivery agents and natural agents could be promising adjuvants for the treatment of periodontitis patients affected or not by cardiovascular disease, diabetes, and other system problems. 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