Extracellular vesicles (EVs) and exosome-like nanovesicles (ELNVs) are natural nanocarriers with unique structural, compositional, and morphological characteristics that provide excellent physical, chemical, and biochemical properties. This review discusses the potential of EVs and ELNVs as oral drug delivery systems, focusing on their therapeutic applications and advancements toward clinical translation. EVs and ELNVs can be derived from milk and plant sources, which offer advantages such as stability in harsh environments and the ability to deliver biotherapeutic macromolecules. Milk EVs have been shown to have significant therapeutic potential, including the delivery of siRNA and mRNA for treating diseases such as Alzheimer's and cancer. ELNVs derived from plants, such as ginger and garlic, have also been investigated for their ability to deliver therapeutic agents and modulate gut microbiota. The study highlights the potential of EVs and ELNVs as promising delivery systems for oral administration, with the ability to target specific cells or tissues and improve drug bioavailability. However, challenges remain in terms of standardization and scalability of these systems for clinical applications. Overall, EVs and ELNVs represent a promising avenue for the development of safe and effective oral drug delivery systems.Extracellular vesicles (EVs) and exosome-like nanovesicles (ELNVs) are natural nanocarriers with unique structural, compositional, and morphological characteristics that provide excellent physical, chemical, and biochemical properties. This review discusses the potential of EVs and ELNVs as oral drug delivery systems, focusing on their therapeutic applications and advancements toward clinical translation. EVs and ELNVs can be derived from milk and plant sources, which offer advantages such as stability in harsh environments and the ability to deliver biotherapeutic macromolecules. Milk EVs have been shown to have significant therapeutic potential, including the delivery of siRNA and mRNA for treating diseases such as Alzheimer's and cancer. ELNVs derived from plants, such as ginger and garlic, have also been investigated for their ability to deliver therapeutic agents and modulate gut microbiota. The study highlights the potential of EVs and ELNVs as promising delivery systems for oral administration, with the ability to target specific cells or tissues and improve drug bioavailability. However, challenges remain in terms of standardization and scalability of these systems for clinical applications. Overall, EVs and ELNVs represent a promising avenue for the development of safe and effective oral drug delivery systems.