The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are key pathological factors in the initiation and progression of vascular disorders, including arteriosclerosis and restenosis following percutaneous coronary intervention (PCI). Hydroxysafflor yellow A (HSYA), the main component of the safflower yellow pigments, has widely been used for the treatment of cardiovascular diseases in traditional Chinese medicine. However, to the best of our knowledge, there are no studies investigating the pharmaceutical effect of HSYA on VSMCs or the underlying molecular mechanism. The present study aimed to investigate the effect of HSYA on platelet‑derived growth factor (PDGF)‑BB‑stimulated VSMC proliferation and migration. HSYA significantly inhibited PDGF‑BB‑stimulated VSMC proliferation and, in response to PDGF‑BB‑stimulation, VSMCs dedifferentiated into a proliferative phenotype. However, HSYA effectively reversed this phenotype switching. In addition, the production of nitrous oxide and cyclic guanosine monophosphate induced by PDGF‑BB was also suppressed by HSYA, and HSYA markedly inhibited PDGF‑BB‑stimulated VSMC migration. Investigation of the molecular mechanism revealed that HSYA inhibited PDGF‑BB‑induced activation of Akt signaling. In addition, HSYA also suppressed PDGF‑BB‑stimulated upregulation of cell cycle related proteins and heme oxygenase‑1. In conclusion, HSYA was able to inhibit PDGF‑BB‑stimulated VSMC proliferation and migration, partially via suppressing PDGF‑BB‑induced Akt signaling activation. Therefore, HSYA may be useful for the prevention and treatment of cardiovascular diseases, including atherosclerosis and restenosis following PCI.