AIM: To identify changes in the salivary protein/peptide profiles by differential proteomics in obese patients with or without periodontitis. MATERIAL AND METHODS: Periodontal examinations and whole saliva samples were obtained from 38 obese patients (mean age: 45.1 ± 7.3 years, mean BMI: 49.3 ± 9 kg/m(2) ) including 13 periodontitis and 25 non-periodontitis subjects, and 19 healthy controls (mean age: 44.2 ± 6.4 years, mean BMI: 21.5 ± 2.1 kg/m(2) ). Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS) was used to compare the whole saliva polypeptide profiles. RESULTS: The SELDI-TOF-MS analysis detected eight putative markers. Six of them were increased and identified in obese subjects versus controls (albumin, α and β haemoglobin chains, α-defensins 1, 2 and 3). Alpha-defensins were less abundant in saliva of periodontitis obese patients (36.47 ± 19.84 μA) versus non-periodontitis obese patients (43.44 ± 30.34 μA), whereas α-defensins were more abundant in obese patients (40.99 ± 26.66 μA) versus controls (27.1 ± 23.98 μA). CONCLUSIONS: Periodontal status modifies the salivary proteome in obese patients. Alpha-defensins may play a role in gingival inflammation, and be involved in the higher susceptibility of obese patients to periodontal diseases.