Objective: Some dipeptidyl peptidase-4 (DPP-4) inhibitor has proven their protective effects on diabetic kidney disease (DKD). The objective of this study was to determine whether gemigliptin, a novel DPP-4 inhibitor developed in Korea, has renoprotective effects in streptozotocin (STZ)-induced type 1 diabetes in mice and study the molecular mechanism in detail. Methods: Diabetes was induced by intraperitoneal administration of a single dose of STZ. Mice with diabetes were treated without or with gemigliptin (300 mg/kg) for 8 weeks. Morphological changes of the glomerular basement membrane (GBM) were observed by electron microscopy and periodic-acid Schiff staining. Then, blood glucose and urinary albumin excretion were measured, and fibrotic markers were detected using immunohistochemical staining, quantitative RT-PCR analysis, and Western blot analysis. Results: Although gemigliptin failed to reduce the blood glucose levels of STZ-treated mice, a significant reduction in urinary albumin excretion and GBM thickness were observed. Immunohistological examination showed that gemigliptin attenuated STZ-induced renal fibrosis and decreased extracellular matrix protein levels, including type 1 collagen and fibronectin, and Smad3 phosphorylation. In cultured rat renal cells, gemigliptin inhibited TGF-b stimulated type 1 collagen and fibronectin mRNA and protein levels via down-regulation of Smad3 phosphorylation. Conclusion: Gemigliptin has renoprotective effects on DKD without eliciting a glucose-lowering effect, suggesting that it harbors therapeutic potential against DKD, including patients with type 1 diabetes.