Exosomes-like nanoparticles can be released by a variety of plants and vegetables. The relevance of plant-derived nanovesicles (PDNVs) in interspecies communication is derived from their content in biomolecules (lipids, proteins, and miRNAs), absence of toxicity, easy internalization by mammalian cells, as well as for their anti-inflammatory, immunomodulatory, and regenerative properties. Due to these interesting features, we review here their potential application in the treatment of inflammatory bowel disease (IBD), liver diseases, and cancer as well as their potentiality as drug carriers. Current evidence indicate that PDNVs can improve the disease state at the level of intestine in IBD mouse models by affecting inflammation and promoting prohealing effects. While few reports suggest that anticancer effects can be derived from antiproliferative and immunomodulatory properties of PDNVs, other studies have shown that PDNVs can be used as effective delivery systems for small molecule agents and nucleic acids with therapeutic effects (siRNAs, miRNAs, and DNAs). Finally, since PDNVs are characterized by a proven stability in the gastrointestinal tract, they have been considered as promising delivery systems for natural products contained therein and drugs (including nucleic acids) via the oral route.