Transcription factor EB (TFEB), which belongs to the microphthalmia/transcription factor E (MiTF/TFE) family, is mainly functioned as regulator involved in regulating lysosomal function and autophagy. It plays an important role in lipid metabolism via modulating lysosomal lipid degradation, mitochondrial β-oxidation of fatty acid, and intracellular cholesterol efflux. TFEB inhibits the development of metabolic associated fatty liver disease (MAFLD) and obesity by regulating the autophagy and the expression of lipid metabolism-related genes. Additionally, it prevents the formation of foam cell from macrophages and vascular smooth muscle cells by restraining lipid accumulation, thereby attenuating the progression of atherosclerosis. TFEB promotes lipophagy to relieve lipid accumulation and lipid accumulation-induced insulin resistance, and β-cell failure, deferring diabetes-related lipid metabolic disorders. In summary, TFEB plays a key role in lipid metabolism and associated lipid disorder diseases, and serves as a potential clinical target to correct lipid dysmetabolism in vivo.