Inspired by blood coagulation and mussel adhesion, we report novel adhesive fibrin-bone@polydopamine (PDA)-shell composite matrix as highly efficient immobilization platform for biomacromolecules and nanomaterials. Fibrin, as a bioglue, and PDA, as a chemical adhesive, are integrated in a one-pot simultaneous polymerization consisting of biopolymerization of fibrinogen and chemical polymerization of dopamine. Fibrin fibers act as adhesive bones to construct scaffold, while PDA coat on the scaffold to form adhesive shell, generating 3D porous composite matrix with unique bone@shell structure. Two types of enzymes (glucose oxidase and acetylcholinesterase) and Au nanoparticles were adopted as respective model biomolecules and nanomaterials to investigate the immobilization capability of the matrix. The bionanocomposites showed high efficiency in capturing nanoparticles and enzymes, as well as significant mass-transfer and biocatalysis efficiencies. Therefore, the bionanocomposites exhibited significant potential in biosensing of glucose and paraoxon with limits of detection down to 5.2 μM and 4 ppt, respectively. The biological−chemical-combined polymerization strategy and composite platform with high immobilization capacity and mass-transfer efficiency open up a novel way for the preparation of high-performance bionanocomposites for various applications, in particular, biosensing.