Lipid droplets (LDs) are intracellular organelles composed of a phospholipid monolayer that store neutral lipids. Although lysosomes contain lysosomal acid lipase (LIPA), the mechanism by which LDs are degraded via microautophagy, and the physiological significance of this process remain poorly understood in mammals. In this study, we found that the cytosolic domain of LAMP2B interacts with phosphatidic acid, facilitating lysosome–LD interactions, leading to the internalization of LDs into lysosomes via microlipophagy. The internalized triacylglycerols (TAGs) are subsequently hydrolyzed by LIPA, and this process is dependent on the ESCRT machinery. Correlative light-electron microscopy (CLEM) visualized the presence of LDs inside lysosomal structures in cells. In vivo experiments using LAMP2B transgenic mice revealed that LAMP2B overexpression attenuated high-fat diet–induced obesity, insulin resistance, and adipose tissue inflammation. Furthermore, lipidomic analysis of liver tissues suggested increased lysosomal TAG hydrolysis upon LAMP2B overexpression. These findings demonstrate that LAMP2B functions as a regulator of microlipophagy in mammals and contributes to the maintenance of lipid metabolic homeostasis.