The roles of miRNAs in the development of cancer have made them promising tools for novel therapeutic approaches. However, the successful delivery of miRNAs to cancer cells has been hampered by difficulties in developing an effective and sustainable delivery mechanism. Exosomes are small endogenous membrane vesicles that mediate communication between cells by delivering genetic materials. Thus, given their intrinsic properties, exosomes have been a focus for use as biological delivery vehicles for miRNAs transfer. Whether exosomes can effectively deliver exogenous miRNAs to pancreatic ductal adenocarcinoma (PDAC) cells has not been thoroughly investigated. Here, we used exosomes from human umbilical cord mesenchymal stromal cells (hucMSCs) to deliver exogenous miR-145-5p, which inhibited PDAC cell proliferation and invasion and increased apoptosis and cell cycle arrest, concomitant with decreased Smad3 expression in vitro. Using a mouse model, we also demonstrated that overexpressing miR-145-5p significantly reduced the growth of xenograft tumors in vivo. Our findings provide novel insights that exosomes might be an attractive therapeutic vehicle for the clinical administration of miRNAs in patients with PDAC.