The plant Dendropanax morbifera Léveille is effective folk medicines for the treatment of several conditions, such as infectious diseases, skin diseases, and other illnesses. Although the inhibitory effects of D. morbifera on the proliferation and migration of vascular smooth muscle cells (VSMCs) have been shown in our previous study, its effects in vivo remain to be elucidated. In this study, we aimed to investigate the protective effects of the extracts from D. morbifera (EDM) on neointimal hyperplasia of rat carotid artery and explore the underlying mechanisms. We observed that the ratio of intima to media thickness (I/M) was significantly decreased in the EDM-treated groups by ~80% compared to that of the control. The expression of Ki-67 and proliferating cell nuclear antigen was decreased by ~70% in the EDM-treated groups compared to that of the control. In addition, matrix metalloproteinase (MMP)2 and MMP9 significantly reduced in the neointimal layer of the EDM-treated groups. Moreover, the decreased levels of contractile phenotypic markers of VSMCs, such as α-smooth muscle actin, myocardin, and smooth muscle-myosin heavy chain, were successfully restored by EDM treatment. Furthermore, the levels of synthetic phenotypic markers, cellular retinal binding protein 1 and connexin 43 were also restored to normal levels. These results suggest that EDM inhibits vascular neointimal hyperplasia induced by balloon injury in rats via phenotypic modulation of VSMCs. Therefore, EDM may be a potential drug candidate for the prevention of restenosis.