Twenty-six exosomal proteins were uniquely identified in the periodontitis group. GO and KEGG analyses revealed enrichment in innate immune response, cytolysis, and complement activation pathways, notably involving C6, C8A, C8B, and CCL28. Western blotting confirmed expression of complement component C6 in salivary exosomes from the periodontitis group. Here, CCL28 is linked to periodontitis.