Abstract Emerging evidence suggests that the ubiquitin‐mediated degradation of insulin‐signalling‐related proteins may be involved in the development of insulin resistance and its related disorders. Tripartite motif‐containing (TRIM) proteins, a superfamily belonging to the E3 ubiquitin ligases, are capable of controlling protein levels and function by ubiquitination, which is essential for the modulation of insulin sensitivity. Recent research has indicated that some of these TRIMs act as key regulatory factors of metabolic disorders such as type 2 diabetes mellitus, obesity, nonalcoholic fatty liver disease, and atherosclerosis. This review provides a comprehensive overview of the latest evidence linking TRIMs to the regulation of insulin resistance and its related disorders, their roles in regulating multiple signalling pathways or cellular processes, such as insulin signalling pathways, peroxisome proliferator‐activated receptor signalling pathways, glucose and lipid metabolism, the inflammatory response, and cell cycle control, as well as recent advances in the development of TRIM‐targeted drugs.