Abstract: Disclosed herein are methods and compositions for disrupting an interaction between Galectin-3 and insulin receptor or glucose transporters. Further disclosed herein are methods and compositions for the treatment of a disease or a disorder in a subject, such as the treatment of diabetes mellitus, insulin resistance, chronic hyperinsulinemia, dysmetabolic syndrome, type A insulin resistance syndrome, type B insulin resistance syndrome, gestational diabetes, acanthosis nigricans, polycystic ovary syndrome (PCOS), obesity, muscle wasting, cardiovascular diseases, cardiac hypertrophy, myocardial ischemia, hypertension, pancreatic cancer associated diabetes (PCDM), rhabdomyosarcoma, or cancers.