Atomic-layered hexagonal boron nitride (hBN) is expected to be the best two-dimensional (2D) anti-oxidation layer on metals for its incomparable impermeability, insulativity, and stability, as well as the progressive bottom-up growth techniques to ensure fast coating on metal surface in large area. However, its real anti-oxidation ability in practice is found to be unsatisfactory and nonuniform, and the main obstacle to achieving ideal anti-oxidation performance lies in unclear anti-oxidation behavior at special interface between 2D hBN and three-dimensional (3D) metals. Herein, system of monolayer hBN grown on copper (Cu) foils with various lattice orientations was grown to investigate the anti-oxidation behavior of different interlayer configurations. By using structural characterizations together with analysis of topography, we surprisingly found that stronger interlayer coupling led to worse anti-oxidation performance owing to fast diffusion of O₂ through higher hBN corrugations generated at the commensurate hBN/Cu(111) configuration. In view of this, we developed the approach of cyclic reannealing that can effectively flatten corrugations and steps, and therefore improve the anti-oxidation performance to a great extent. This work provides a more in-depth understanding of anti-oxidation behavior of 2D materials grown on 3D metals, and a practical method to pave the way for its large-scale applications in future.