New organelle acquisition through neofunctionalization of the endomembrane system (ES) with respect to plant secondary metabolism is a key evolutionary strategy for plant adaptation, which is overlooked due to the complexity of angiosperms. Bryophytes produce a broad range of plant secondary metabolites (PSMs), and their simple cellular structures, including unique organelles, such as oil bodies (OBs), highlight them as suitable model to investigate the contribution of the ES to PSMs. In this opinion, we review latest findings on the contribution of the ES to PSM biosynthesis, with a specific focus on OBs, and propose that the ES provides organelles and trafficking routes for PSM biosynthesis, transportation, and storage. Therefore, future research on ES-derived organelles and trafficking routes will provide essential knowledge for synthetic applications.