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Octenidine dihydrochloride is an antimicrobial cationic surfactant compound. We conducted a systematic review to determine the efficacy of octenidine-based mouthwash on plaque formation, gingivitis, and oral microbial growth in subjects with or without periodontal disease. PubMed/MEDLINE, ScienceDirect, Google Scholar, and Cochrane Library were searched for relevant studies. The review was conducted per PRISMA guidelines. Only randomized controlled trials and observational studies comparing octenidine with placebo or other mouthwashes i