• MSC-EVs offer a cell-free therapeutic approach for T2D by modulating inflammation, promoting tissue regeneration, and improving insulin resistance.
• Engineering strategies, including optimized culture conditions, cargo modification, and bioactive material-based delivery systems, enhance MSC-EV yield, quality, and therapeutic efficacy.
• Key challenges for clinical translation include limited yield, heterogeneity, long-term safety, immunocompatibility, and scalable production of MSC-EVs.
• Artificial intelligence is highlighted as a promising tool to guide future research and overcome barriers in MSC-EV-based T2D therapy.