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A comprehensive search was conducted in the Embase, PubMed, Scopus, Web of Science, EBSCO, Cochrane, LILACS databases, and in gray literature sources (ProQuest and Google Scholar) up to September 2024. Clinical studies evaluating the reduction of microbial load (CFU) on complete dentures after chlorhexidine use across different concentrations, vehicles, and application protocols were included. Study selection and data extraction were performed by two independent reviewers. Risk of bias of included studies was assessed with the Joanna Briggs Institute checklist. Meta-analysis was conducted to compare the antimicrobial efficacy of different protocols (RevMan). The certainty of evidence was assessed using GRADEpro-GDT. A total of twenty-two studies were included (\u03ba\u2009=\u20090.877), and five met the criteria for inclusion in the meta-analysis. Interventions included immersion, mouth rinses, sprays, and topical application, with chlorhexidine concentrations ranging from 0.12% to 4%. Chlorhexidine showed a significant reduction in CFU counts, with mean differences of -1.11 (95% CI: -1.57 to -0.64;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.00001) for 0.12% up to 7 days, and \u2212\u20092.50 (95% CI: -4.57 to -0.43;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02) for 0.2% up to 30 days. The pooled analysis of both concentrations also revealed a significant microbial reduction (CFU\/mL) over time of -1.66 (95% CI: -2.75 to -0.57;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.003). Chlorhexidine demonstrated effectiveness in disinfecting complete dentures regardless of concentration and mode of use. However, despite the favorable outcomes, further standardized clinical studies are needed to establish optimized and reproducible protocols for dental practice.\n                  <\/jats:p>","DOI":"10.1007\/s10266-026-01408-1","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T21:13:53Z","timestamp":1780434833000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chlorhexidine-based protocols for complete denture disinfection: a systematic review and meta-analysis"],"prefix":"10.1007","author":[{"given":"Artur Ferronato","family":"Soto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eduarda Broering","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique Souza","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana Pinto","family":"Bezerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otavio Marino","family":"dos Santos Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiane Machado","family":"Mengatto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edilaine Braschi","family":"Moretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Guerra","family":"Lund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Silva Ribeiro","family":"de Andrade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maur\u00edcio Malheiros","family":"Badar\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"1408_CR1","unstructured":"World Health Organization. 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