AIMS: To investigate the effects of non-surgical periodontal treatment on the levels of cytokines, sIgA, antimicrobial peptides, oxidative and antioxidative agents in comparison between patients with and without diabetes. METHODS: A case-control study that included patients (n = 45) with periodontitis who have or do not have diabetes. Cytokine concentrations in crevicular gingival fluid (GCF) and saliva were determined using LUMINEX and ELISA assays, respectively. Salivary levels of lysozyme, cathelicidin (LL-37), total antioxidant capacity (TAC) and total peroxide were determined colorimetrically before (T0) and one month after completion of periodontitis treatment (T1). RESULTS: There were no significant differences in the concentrations of cytokines in GCF between the groups and T0 and T1. Salivary concentrations of lysozyme and IL-10 were significantly reduced in T1 compared to T0 in the diabetes group (p = 0.0260 and p = 0.0034, respectively), whilst TNF-α concentration was higher in T1 (p = 0.0443). The salivary concentrations of TNF-α observed in the non-diabetes group at T1 decreased at T0 (p = 0.0313). The salivary concentration of TNF-α was increased in the diabetes group compared to the non-diabetes group at T1 (p = 0.0008). CONCLUSIONS: An improvement in salivary inflammatory status was observed in the group without diabetes, which was not found in the group with diabetes after non-surgical periodontal treatment.