Bioavailability is an eternal topic that cannot be circumvented by peroral drug delivery. Adequate blood drug exposure after oral administration is a prerequisite for effective treatment. Nanovesicles as pleiotropic oral vehicles can solubilize, encapsulate, stabilize an active ingredient and promote the payload absorption via various mechanisms. Vesicular systems with nanoscale size, such as liposomes, niosomes and polymersomes, provide a versatile platform for oral delivery of drugs with distinct nature. The amphiphilicity of vesicles in structure allows hydrophilic and lipophilic molecule(s) either or both to be loaded, being encapsulated in the aqueous cavity or the inner core, respectively. Depending on high oral transport efficiency based on their structural flexibility, gastrointestinal stability, biocompatibility, and/or intestinal epithelial affinity, nanovesicles can markedly augment the oral bioavailability of various poorly absorbed drugs. Vesicular drug delivery systems (VDDSs) demonstrate a lot of preferences and are becoming more prominent of late years in biomedical applications. Equally, these systems can potentiate a drug's therapeutic index by ameliorating the oral absorption. This review devotes to comment on various VDDSs with special emphasis on the peroral drug delivery. The classification of nanovesicles, preparative processes, intestinal transport mechanisms, in vivo fate, and design rationale were expounded. Knowledge on vesicles-mediated oral drug delivery for bioavailability enhancement has been properly provided. It can be concluded that VDDSs with many merits will step into an energetic arena in oral drug delivery.© 2022 Ren et al.