AbstractThe ubiquitin‐proteasome system, which is one of the systems for cell protein homeostasis and degradation, happens through the ordered and coordinated action of three types of enzymes, E1 ubiquitin‐activating enzyme, E2 ubiquitin‐carrier enzyme, E3 ubiquitin‐protein ligase. Tripartite motif‐containing (TRIM) family proteins are the richest subfamily of really interesting new gene E3 ubiquitin ligases, which play a critical role not only in many biological processes, including proliferation, apoptosis, pyroptosis, innate immunity, and autophagy, but also many diseases like cancer, diabetes mellitus, and neurodegenerative disease. Increasing evidence suggests that TRIM family proteins play a vital role in modulating autophagy, pyroptosis, and diabetes mellitus. The aim of this review is to discuss the role of TRIM proteins in the regulation of autophagy, pyroptosis, diabetes mellitus, and diabetic complications.