New strategies are needed to combat diabetes-induced heart and kidney disease. We have identified a novel target, called insulin regulated aminopeptidase (IRAP), and have developed new drugs that inhibit the action of IRAP. This study demonstrated that treatment with our novel drugs was more effective than use of a current gold standard of care treatment to alleviate the tissue fibrosis and remodelling that occurs in diabetes-induced heart and kidney disease, with multiple actions of IRAP inhibition involved in mediating the protective effects. Overall, targeting IRAP shows promise as an effective treatment to combat diabetes-induced heart and kidney disease.