The limitation of short-term usage of neural interfacing devices encouraged the development of neuro-specific biomaterials. Our hypothesis is that a biomaterial covered with the neuronal cell-derived membrane possessing neural cell adhesion molecule (L1CAM) can promote neuronal adhesion and activation and minimize immune responses at the condition of neural implantation. To demonstrate the hypothesis, we prepared the titanium surface-modified with a PC12 cell membrane-derived lipid bilayer, covalently tethered on the surface (PM-TLB). Anti-fouling studies informed us that PM-TLB was sufficiently resistant to the fouling of plasma proteins as well as the adhesion of blood components and bacteria. Cell studies demonstrated that PM-TLB is specific to neuronal cells and non-specific to astrocytes and macrophages, clearly shown in a normal condition and an inflammatory condition. The neuronal activation study supported that PM-TLB improves the outgrowth of neurites and activation stages more than the poly(l-lysine) polymer, which is the most used substrate for neuronal cells. These results conclude that PM-TLB is an efficient surface modification showing selective modulation against neurons and the immune system, promoting neuronal interaction and suppressing neuro-inflammatory responses for applications to neuro-implantable devices.