In this work, a novel biomimetic surface‐attachable initiator is successfully synthesized by the conjugation of 3,4‐dihydroxyphenylacetic acid and thermal 2,2′‐azobis(2‐methylpropionamide) dihydrochloride (V‐50). The synthesized initiator (DOPV) can adhere to various material surfaces in a mussel‐inspired way and initiate the surface grafting polymerization. Hydrogel coatings are facilely prepared by the thermal‐initiated radical copolymerization of antimicrobial polyhexamethylene guanidine and antifouling polyethylene glycol oligomers. The developed hydrogel coatings not only show antimicrobial activity toward gram‐negative and gram‐positive bacteria but also demonstrate protein resistance, antibiofilm efficacy, hemocompatibility, and low cytotoxicity in vitro. Most importantly, the hydrogel coatings reveal excellent antimicrobial efficacy with a log reduction above 5 in a rodent subcutaneous infection model. These results demonstrate the potential fabrication of bio‐functional coatings for biomedical devices or implants through an inexpensive, facile, and environmentally friendly mussel‐inspired technique.