Autoimmune diseases (AID) encompass a diverse array of conditions characterized by immune system dysregulation, resulting in aberrant responses of B cells and T cells against the body’s own healthy tissues. Plant extracellular vesicles (PEVs) are nanoscale particles enclosed by phospholipid bilayers, secreted by plant cells, which facilitate intercellular communication by transporting various bioactive molecules. Due to their nanoscale structure, safety, abundant sources, low immunogenicity, high yield, biocompatibility, and effective targeting of the colon and liver, PEVs are regarded as a promising platform for the treatment of AID. This review provides a comprehensive summary of PEV biogenesis, physicochemical and biological properties, internalization mechanisms, isolation methods, and their applications in various diseases, with a specific focus on their potential roles in AID. Additionally, we propose engineering approaches and administration methods for PEVs. Finally, we present an overview of the advantages and challenges associated with utilizing PEVs for the treatment of AID. By gaining a comprehensive understanding of PEVs, we anticipate the development of innovative therapeutic strategies for AID. Natural and engineered PEVs hold substantial promise as a valuable resource for innovative technologies in AID treatment.