This work developed innovative poly(ester-urethane) materials double-modified by quercetin (QC) and phosphorylcholine (PC) with improved antibacterial activity and hemocompatibility. The functional monomer of PC-diol was first synthesized via a click reaction between 2-methacryloyloxyethyl phosphorylcholine and α-thioglycerol; the NCO-terminated prepolymer was subsequently prepared by a one-pot condensation method of PC-diol, poly(ε-caprolactone) diol, and excess isophorone diisocyanate; finally, the prepolymer was chain-extended with QC to produce the linear products (PEU-PQs). 1H NMR, FT-IR, and XPS techniques confirmed the successful introduction of PC and QC, and the in-depth characterization of the cast PEU-PQ films was carried out. Although a low crystallinity was demonstrated by XRD and thermal analysis, the films exhibited excellent tensile stress and stretchability due to the interchain multiple hydrogen bonds. The introduction of PC groups enhanced the surface hydrophilicity, water absorption, and the in vitro hydrolytic degradation rate of the film materials. Inhibition zone tests presented that the QC-based PEU-PQs had effective antibacterial activity against E. coli and S. aureus. The biological evaluations of the materials were performed in vitro by protein absorption, platelet adhesion, and cytotoxic test and in vivo by subcutaneous implantation, which demonstrated superior surface hemocompatibility and biocompatibility. Collectively, the PEU-PQ biomaterials hold a prospective application in durable blood-contacting devices.