The femtosecond laser processing technology primarily uses the laser focus to eliminate the microzone of the material. The exact processing of diverse functional microstructures is possible when combined with the precision design of the processing route and fine laser parameter control. However, during processing, the material's surface is not always in an ideal plane, which changes the distance between the laser focus and the material's surface. This results in the material's surface receiving a laser focal spot of varying sizes, which causes the microstructure of femtosecond laser processing to be uneven and, ultimately, does not meet the requirements of some applications. To address this problem, two calibration methods based on sub-region plane fitting and two-dimensional interpolation are proposed. First, the surface topography of the material is approximately described by a small number of sampling points in the area to be processed. Based on this, the processing path's height coordinates are adjusted to ensure that the processing impact is not adversely affected by the relative distance between the laser focus and the material surface during femtosecond laser processing. The experimental results demonstrate that these two calibration techniques are efficient ways to address the issue that non-flat surfaces make it challenging to achieve high-quality microstructure processing by femtosecond laser. They can ensure the uniformity and consistency of large-area microstructures processed by femtosecond laser.