In the development of cardiovascular diseases, vascular smooth muscle cells (VSMCs) undergo transition from a contractile to a synthetic phenotype. Notch- and Wnt-dependent signaling pathways play a critical role during this process. Curcumin has potential for clinical use including anti-inflammatory and antitumor actions. However, the effect of curcumin on VSMC phenotype transition remains unclear. In VSMCs isolated from the thoracic aorta of Sprague Dawley rats, curcumin (5–20 μM) produced a concentration-dependent inhibition of serum-elicited VSMC migration. Furthermore, curcumin, at the dose of 20 μM, partially reversed the repression of VSMC markers induced by serum stimulation, an effect associated with attenuation of Jagged-1 and Notch-1 levels and downregulation of the downstream gene Hey-1. Downregulation of Wnt-4 was also observed after curcumin treatment in the presence of serum, which was followed by inhibition of nuclear β-catenin translocation and cyclin D1 expression. These data suggest that curcumin is a potent regulator of VSMCs phenotype transition and may play a critical role in regulating these events after vascular injury.