This systematic review offers a comprehensive analysis of plant-derived extracellular vesicles (PDEVs) as emerging drug delivery systems, focusing on original research articles published between 2016 and 2024 that exclusively examine the use of PDEVs for drug delivery. After a rigorous search across multiple databases, 20 relevant studies out of 805 initial results were selected for analysis. This review systematically summarizes the critical data on PDEV components, isolation methods, and drug-loading techniques. It highlights the potential of PDEVs to significantly enhance drug safety and efficacy, reduce dosage and toxicity, and align drug development with sustainable and environmentally friendly biotechnological processes. This review also emphasizes the advantages of PDEVs over mammalian-derived vesicles, such as cost-effectiveness, higher yield, and reduced immunogenicity. Additionally, it explores the synergistic potential between encapsulated drugs and bioactive compounds naturally present in PDEVs. This study acknowledges the challenges in standardizing isolation and formulation methods for clinical use. Overall, this review provides valuable insights into the current state and future directions of PDEV-based drug delivery systems, highlighting their promising role in advancing pharmaceutical research and development.