The first maleimide-functionalized poly-p-xylylene is synthesized via chemical vapor deposition (CVD) polymerization from 4-N-maleimidomethyl-[2,2]paracyclophane on various substrates. Coated substrates are readily available to perform thiol–maleimide click reaction under mild conditions. Designed surfaces are highlighted in low-protein-fouling modification as well as manipulated attachments and growth of bovine arterial endothelial cells. The availability of the maleimide functionality is further exploited in combination with alkynyl moiety, and the direct synthesis to prepare the multicomponent coating containing the two functionalities is enabled via CVD copolymerization on various substrates. The novel coating is comprised of distinguished anchoring sites of electron-deficient alkynes and unsaturated maleimides and is readily to simultaneously proceed doubled “click” reactions. XPS and IRRAS characterizations have verified the chemical composition for the coatings. The demonstration of synergically doubled bioorthogonal reactions is performed via azide-alkyne click reaction and thiol-maleimide coupling reaction to immobilize fluorescently labeled azides and cystines, respectively, under mild conditions in water and without the need of a catalyst, and no trace of cross-reaction is found. Finally, the multicomponent surface is designed to exhibit distinct biological functions by first immobilizing polyethylene glycols that provide a low fouling state (bioinert) to suppress undesired background perturbance, while at the same time, addressing surface bioactive function is performed by tethering Cys-Arg-Glu-Asp-Val (CREDV) peptides on stent substrate and the adhesion of human umbilical vein endothelial cells (HUVECs) are precisely manipulated.