Background: Plant-derived exosome-like nanoparticles (PELNs) are nanoscale vesicles secreted by plant cells that contain lipids, proteins, RNAs, and secondary metabolites. Increasing evidence indicates that these vesicles can deliver plant-derived molecules into mammalian cells and modulate biological processes, including inflammation, oxidative stress, and immune responses. Scope of the Review: This review summarizes current knowledge of PELNs, including their biogenesis, molecular composition, isolation and characterization strategies, cellular uptake mechanisms, and reported therapeutic applications. Representative examples from medicinal plants, such as ginger (Zingiber officinale), turmeric (Curcuma longa), and tea (Camellia sinensis), are discussed to illustrate their biological activity and their potential as natural nanocarriers. Their physicochemical stability, biocompatibility, and low immunogenicity support ongoing investigation for both oral and systemic delivery. Challenges and Future Prospects: Despite growing interest, several challenges remain, including the lack of standardized isolation and purification protocols, variability in vesicle composition, and limited regulatory frameworks. Advances in omics-based analyses and functional validation will be essential to clarify mechanisms of action and improve reproducibility. Conclusion: PELNs represent a rapidly developing research area at the interface of natural products and nanomedicine. Although current evidence is largely preclinical, these vesicles may contribute to the development of safe and effective therapeutic strategies with further validation.