In this study, a nanobiocatalyst [α-amylase/γaminopropyltriethoxysilane-modified silica nanoparticles (A-SNPs)] was prepared for efficient mudcake removal and reservoir damage control during horizontal drilling and openhole completion. The molecular structure, thermal stability, and colloidal properties of the nanobiocatalyst were characterized by using FTIR, TGA, particle size, zeta potential, SEM, and TEM tests. The results confirmed that A-SNPs were securely encapsulated on the surface of α-amylase via covalent imine bonding (C�N), significantly enhancing the stability of αamylase. Mudcake and polymer plugging removal experiments demonstrated that soaking mudcake in a 1% nanobiocatalyst solution for 4 h reduced the filtrate return time to under 10 min. Additionally, polymer removal efficiency exceeded 63.17% at 500 psi. Core flow experiments combined with NMR analysis revealed that the nanobiocatalyst effectively mitigated permeability damage at 95 °C, achieving a core permeability restoration value of 82.88%. The nanobiocatalyst significantly reduced the fluid flow resistance and improved hydrocarbon availability within the reservoir porous medium. In conclusion, nanobiocatalysts have great potential for application in oil and gas drilling and hydrocarbon recovery.