Neointimal hyperplasia (or restenosis) is primarily attributed to excessive proliferation and migration of vascular smooth muscle cells (VSMCs). In this study, we investigated the inhibitory effects and mechanisms of ugonin J on VSMC proliferation and migration as well as neointimal formation. Cell viability and the cell‐cycle distribution were, respectively, analyzed using an MTT assay and flow cytometry. Cell migration was examined using a wound‐healing analysis and a transwell assay. Protein expressions and gelatinase activities were, respectively, measured using Western blot and gelatin zymography. Balloon angioplasty‐induced neointimal formation was induced in a rat carotid artery model and then examined using immunohistochemical staining. Ugonin J induced cell‐cycle arrest at the G0/G1 phase and apoptosis to inhibit VSMC growth. Ugonin J also exhibited marked suppressive activity on VSMC migration. Ugonin J significantly reduced activations of focal adhesion kinase, phosphoinositide 3‐kinase, v‐akt murine thymoma viral oncogene homolog 1, and extracellular signal‐regulated kinase 1/2 proteins. Moreover, ugonin J obviously reduced expressions and activity levels of matrix metalloproteinase‐2 and matrix metalloproteinase‐9. In vivo data indicated that ugonin J prevented balloon angioplasty‐induced neointimal hyperplasia. Our study suggested that ugonin J has the potential for application in the prevention of balloon injury‐induced neointimal formation.