Extracellular vesicles (EVs) play a crucial role in intercellular communication and have the potential to serve as in vivo carriers for delivering active molecules. The biocompatibility advantages of EVs over artificial nanocarriers create new frontiers for delivering modern active molecules. Milk is a favorable source of EVs because of its high bioavailability, low immunogenicity, and commercial producibility. In this study, we analyzed the advantages of milk-derived EVs in the oral delivery of active molecules, discussed their research progress in delivering active phytoconstituents, and summarized the necessary technologies and critical unit operations required for the development of an oral delivery system based on EVs. The review aims to provide innovative ideas and fundamental quality control guidelines for developing the next-generation oral drug delivery system based on milk-derived EVs. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 15 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.