Plant-derived exosome-like nanovesicles (PELNs) from edible plants, isolated by ultracentrifugation, size exclusion chromatography or other methods, were proved to contain a variety of biologically active and therapeutically specific components. Recently, investigations in the field of PELN-based biomedicine have been conducted, which positioned those nanovesicles as promising tools for prevention and treatment of several diseases, with their natural origin potentially offering superior biocompatibility and bioavailability. However, the inadequate targeting and limited therapeutic effects constrain the utility and clinical translation of PELNs. Thus, strategies aiming at bridging the gap by engineering natural PELNs have been of great interest. Those approaches include membrane hybridization, physical and chemical surface functionalization and encapsulation of therapeutic payloads. Herein, we provide a comprehensive overview of the biogenesis and composition, isolation and purification methods and characterization of PELNs, as well as their therapeutic functions. Current knowledge on the construction strategies and biomedical application of engineered PELNs were reviewed. Additionally, future directions and perspectives in this field were discussed in order to further enrich and expand the prospects for the application of engineered PELNs.