Curcumin, a hydrophobic polyphenol derived from turmeric, has been used a food additive and as a herbal medicine for the treatment of various diseases, but the clinical application of curcumin is restricted by its poor aqueous solubility and its low permeability and bioavailability levels. In the present study, we investigate the functional role of a nanosphere loaded with curcumin (CN) in the promotion of the motility of human mesenchymal stem cells (MSCs) during the skin wound healing process. CN significantly increased the motility of umbilical cord blood (UCB)-MSCs and showed 10,000-fold greater migration efficacy than curcumin. CN stimulated the phosphorylation of c-Src and protein kinase C which are responsible for the distinctive activation of the MAPKs. Interestingly, CN significantly induced the expression levels of α-actinin-1, profilin-1 and filamentous-actin, as regulated by the phosphorylation of nuclear factor-kappa B during its promotion of cell migration. In a mouse skin excisional wound model, we found that transplantation of UCB-MSCs pre-treated with CN enhanced wound closure, granulation, and re-epithelialization at mouse skin wound sites. These results indicate that CN is a functional agent that promotes the mobilization of UCB-MSCs for cutaneous wound repair.