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After the identification of the DEPs reported by the included human primary studies, gene ontology (GO), the Kyoto encyclopedia of genes and genomes pathway (KEGG), protein\u2013protein interaction (PPI), and meta\u2010analyses were conducted. The risk of bias among the included studies was evaluated using the modified Newcastle\u2013Ottawa quality assessment scale.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The review identified significant differences in protein expression between healthy individuals and those with gingivitis and periodontitis. In GCF, 247 proteins were upregulated and 128 downregulated in periodontal diseases. Saliva analysis revealed 79 upregulated and 70 downregulated proteins. There were distinct protein profiles between gingivitis and periodontitis, with 159 and 31 unique upregulated proteins in GCF, respectively. Meta\u2010analyses confirmed significant upregulation of various proteins in periodontitis, including <jats:italic>ALB<\/jats:italic> and <jats:italic>MMP9<\/jats:italic>, while <jats:italic>CSTB<\/jats:italic> and <jats:italic>GSTP1<\/jats:italic> were downregulated. <jats:italic>AMY1A<\/jats:italic> and <jats:italic>SERPINA1<\/jats:italic> were upregulated in periodontitis saliva. HBD was upregulated in gingivitis GCF, while <jats:italic>DEFA3<\/jats:italic> was downregulated. PPI analysis revealed complex networks of interactions among DEPs. GO and KEGG pathway analyses provided insights into biological processes and pathways associated with periodontal diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The ongoing MS\u2010based proteomics studies emphasize the need for a highly sensitive and specific diagnostic tool for periodontal diseases. Clinician acceptance of the eventual diagnostic method relies on its ability to provide superior or complementary information to current clinical assessment procedures. 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