Saliva, gingival crevicular fluid (GCF), and serum are common sources for studying host response and oral microbiota in periodontal patients. This cross-sectional study aimed to compare the proteomic signatures of periodontitis patients using full-mouth periodontal sampling with those obtained from serum and saliva samples. This study analysed proteome profiles from these biological sources in three systemically healthy, non-smoking patients with stage III, and grade C periodontitis.