Curcumin has diverse pharmacological activities but poor water solubility, rapid degradation, extensive metabolism, and very low oral bioavailability limit its therapeutic use. This review evaluates mesenchymal stem cell-derived exosomes (MSC-Exo; MSC-derived small extracellular vesicles per MISEV2023) as natural nanocarriers for curcumin delivery and the barriers to clinical translation. Curcumin-loaded MSC-Exo (Cur@Exos) can improve curcumin stability, sustain release, enhance target-tissue accumulation, and cross biological barriers such as the blood-brain barrier. Compared with synthetic nanocarriers, MSC-Exo may offer better biocompatibility, immune evasion, and tissue tropism, but these properties depend on source and preparation; proteomes, miRNA cargoes, and functions differ among bone marrow-, umbilical cord-, and adipose-derived MSCs. Encapsulation efficiency, batch consistency, scalability, and storage stability also remain suboptimal. Preclinical studies show Cur@Exos benefits in neurodegenerative diseases, rheumatoid arthritis, liver disease, wound healing, bone defects, and sepsis-associated kidney injury. However, findings are limited by heterogeneity in exosome sources, preparation, loading methods, and animal models; small samples and short follow-up; inconsistent dose metrics (particle number vs. protein content); and lack of standardized process and outcome criteria, reference materials, and potency assays. Long-term safety remains inadequately established: current evidence covers only short-term single or repeated dosing; ≥ 6-month repeat-dose toxicology with anti-drug antibody and complement monitoring, predictive immunogenicity screening, tumorigenicity assessment, potency-based batch release testing, and clinical efficacy data are lacking. MSC-Exo is a promising curcumin-delivery platform, but translation requires standardized manufacturing, globally harmonized quality control, improved scalability, systematic safety evaluation, well-designed multicenter trials, and a clarified international regulatory pathway.