In this paper, a novel and biocompatible approach for fluorescent nanodiamond (FND) biofunctionlization is proposed by facile enzyme catalysis. Specifically, the fluorescent nanodiamond is treated by Cytochrome P450 (CYP) to conjugate with anti-immunoglobulin G (anti-IgG). With low concentration hydrogen peroxide, the enzyme catalysis increases the oxidation degree of nanodiamond and retains the high biocompatibility nature of nanodiamond. Consequently, the increasing oxygen containing groups on the nanodiamond enhance its stability and solubility in water, which are beneficial for nanodiamond covalent functionalized with biomolecules. Based on the experimental results from Scanning Electron Microscopy (SEM), UV-vis spectrophotometer, Fourier Transforms Infrared Spectroscopy (FTIR), and Fluorescence Microscopy, anti-IgG is successfully immobilized on the CYP catalyzed nanodiamond and maintains its superior fluorescence property.