• Dihydrolipoic acid-modified sulfobetaine derived starch hydrogel coatings are fabricated. • Hydrogel coatings can resist cell and tissue adhesion, prevent thrombosis, and alleviate inflammation response in vivo . • Hydrogel coatings exhibit excellent long-term durability and stability. • Hydrogel coatings can selectively promote the adhesion, proliferation, and migration of HUVECs. Zwitterionic polymers coating shows significant advantages in preventing thrombosis for the treatment of cardiovascular diseases. However, their limited bio-functionality and low durability struggle to meet requirements from clinical applications. In this study, a dihydrolipoic acid-modified sulfobetaine-derived starch (SB-ST-D) hydrogel coating is developed for polyethylene terephthalate (PET) based blood-contacting devices. First, polydopamine (PDA) is deposited on the PET surface (PDA/PET). Then, SB-ST-D is covalently immobilized on the surface of the PDA/PET (SSD/PET) via Michael addition reaction and the hydrogel is formed by the disulfide bridge formation. The obtained SB-ST-D hydrogel coatings not only exhibit excellent biocompatibility, but also effectively resist non-specific protein adsorption, inhibit cell and platelet adhesion, prevent thrombosis, and alleviate inflammation response in vivo . Moreover, the SB-ST-D hydrogel coating can maintain good anti-fouling properties after 45 d of immersion in PBS, 7 d of PBS buffer shearing, and even under mechanical damage. To improve the specific adhesion capacity of human umbilical vein endothelial cells (HUVECs), the REDV is introduced on the SB-ST-D coating surface via thiol–ene click reaction. Results suggest that the obtained coating can promote the adhesion, proliferation, and migration of HUVECs, and decrease the adhesion of human aortic smooth muscle cells simultaneously. Therefore, the prepared SB-ST-D hydrogel coatings with combined durable, antithrombotic, and bio-functional properties will be a milestone in the development of long-term blood-contacting devices.