Aims: This study aimed to investigate the impacts of synbiotic supplementation in Type 2 Diabetes Mellitus (T2DM) Patients with Chronic Periodontitis (CP) under non-surgical periodontal therapy (NSPT). Materials and Methods: In this study 47 patients suffering from DM and CP were recruited and randomly assigned to two groups. The intervention (n= 23) and control (n=24) groups received either multispecies probiotic supplement plus 100 mg fructo-oligosaccharide (500 mg in each capsule) or placebo capsule containing 500 mg wheat flour respectively every day for 8 weeks. All subjects were treated with NSPT during the intervention period. Serum levels of interleukin- 1β (IL-1β), malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and periodontal indices including clinical attachment loss (CAL), pocket depth (PD), BOP, and plaque were measured before and after the intervention. All statistical analysis was performed using SPSS (version 19; SPSS Inc., Chicago, IL). All results were expressed as means ± standard deviations (SD) for quantitative variables or number (percentage) for qualitative variables. To ensure a normal distribution of variables Kolmogorov-Smirnoff test was used. Chi-square test was used to compare qualitative variables. Paired-sample test was used to identify withingroup differences (before and after intervention). We used Independent sample t-test to compare the results between the two groups (placebo and synbiotic supplement). Also, Independent T-test was used to identify changes between two groups at the end of study. Results with P < 0.05 were considered statistically significant.Results: Supplementation with the synbiotic with NSPT led to a significant decrease in the mean levels of IL-1β, MDA, PD and CAL in the intervention group post-intervention (p < 0.05). The serum levels of TAC, SOD, and GPx were significantly increased in the intervention group compared with the baseline (p < 0.05). Consumption of synbiotic withNSPT, compared to the control, resulted in a significant decrease in the mean changes of IL-1β, MDA, and CAL. Also, the mean changes of TAC and GPx were significantly higher in the intervention group compared with the control group (p < 0.05) Conclusions: It was observed that synbiotic supplementation with NSPT may be beneficial in improving inflammatory, antioxidant, and periodontal status in T2DM patients with CP .