This study determined the effects of probiotic supplementation on glycemic control, lipid concentrations, biomarkers of inflammation and oxidative stress in 60 diabetic patients on hemodialysis in a parallel randomized double-blind placebo-controlled clinical trial. Participants were initially matched based on sex, duration of dialysis and diabetes, body mass index and age. Subsequently, they were randomly divided into two groups to take either a capsule containing the probiotics Lactobacillus acidophilus , Lactobacillus casei and Bifidobacterium bifidum or placebo for 12 weeks. Based on three-day dietary records throughout the trial, there was no significant change in dietary macro- and micro-nutrients or total dietary fiber to confound results. After the 12 weeks, analysis of patients who received probiotic supplements compared with the placebo showed they had significantly decreased fasting plasma glucose (–22.0 vs. +6.6 mg/dl), serum insulin (–6.4 vs. +2.3 μIU/ml), homeostasis model of assessment-estimated insulin resistance (–2.9 vs. +2.5), homeostasis model of assessment-estimated beta-cell function (–14.1 vs. +6.1) and HbA1c (–0.4 vs. –0.1%,), and improved quantitative insulin sensitivity check index (+0.03 vs. –0.02). Additionally, compared with the placebo, probiotic supplementation resulted in significant reductions in serum high-sensitivity C-reactive protein (–1933 vs. +252 ng/ml), plasma malondialdehyde (–0.3 vs. +1.0 μmol/l), subjective global assessment scores (–0.7 vs. +0.7) and total iron binding capacity (–230 vs. +33 μg/dl), and a significant increase in plasma total antioxidant capacity (+15 vs. –88 mmol/l). Thus, probiotic supplementation for 12 weeks among diabetic hemodialysis patients had beneficial effects on parameters of glucose homeostasis, and some biomarkers of inflammation and oxidative stress.