AbstractDiabetes mellitus (DM) is a worldwide disease that affects 9% of the adult world population and type 2 DM accounts for 90% of those. A common consequence of DM is kidney complications, which could lead to kidney failure. We studied the potential effects of treatment with insulin and the glucagon‐like peptide 1 receptor (GLP‐1R) agonist liraglutide on the diabetic kidney proteome through the use of the db/db mouse model system and mass spectrometry (MS). Multivariate analyses revealed distinct effects of insulin and liraglutide on the db/db kidney proteome, which was seen on the protein levels of, for example, pterin‐4 α‐carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor‐1α (PCBD1), neural precursor cell expressed developmentally down‐regulated‐8 (NEDD8), transcription elongation factor‐B polypeptide‐1 (ELOC) and hepcidin (HEPC). Furthermore, the separation of the insulin, liraglutide and vehicle db/db mouse groups in multivariate analyses was not mainly related to the albumin excretion rate (AER) or the level of glycated hemoglobin A1c (HbA1c%) in the mice. In summary, we show that insulin and liraglutide give rise to separate protein profiles in the db/db mouse kidney.