Inflammation and glycemic control are important prognosis-related factors for hemodialysis (HD) patients; moreover, inflammation affects insulin secretion. Here, we evaluated the anti-inflammatory effects of monotherapy with linagliptin—a dipeptidase-4 inhibitor—in HD patients with type 2 diabetes. We examined 21 diabetic HD patients who were not receiving oral diabetes drugs or insulin therapy and with poor glycemic control (glycated albumin [GA] level, >20%). Linagliptin (5 mg) was administered to the patients daily. The levels of prostaglandin E2 (PGE2), interleukin-6 (IL-6), high-sensitivity C-reactive protein, GA, blood glucose, and active glucagon-like peptide-1 were determined before and 6 months after treatment. Body weight and serum levels of albumin, hemoglobin, total cholesterol, and low-density lipoprotein cholesterol were also recorded before and after treatment. The levels of PGE2 and GA were significantly decreased 1 month after starting linagliptin therapy, whereas the IL-6 levels were significantly decreased 6 months after starting linagliptin therapy. After 6 months of treatment, the PGE2 levels decreased from 188 ± 50 ng/mL to 26 ± 5 ng/mL; IL-6 levels, from 1.5 ± 0.4 pg/mL to 0.6 ± 0.1 pg/mL; and GA levels, from 21.3% ± 0.6% to 18.0% ± 0.6%. Glucagon-like peptide-1 levels increased 2.5-fold during the treatment. Over the 6-month treatment period, body weight and levels of high-sensitivity C-reactive protein, blood glucose, albumin, hemoglobin, and cholesterol did not change; none of the patients exhibited hypoglycemia. The anti-inflammatory effects of linagliptin monotherapy indicate that it may serve as a useful glucose control strategy for HD patients with diabetes.