In order to accurately model the machine-lunar soil simulant interaction, this study combined physical and simulation experiments to calibrate the discrete element simulation parameters of the JLU-H lunar highland simulant. First, the intrinsic parameters and the true angle of repose of the JLU-H were determined through physical tests to provide data for subsequent simulation tests. A Plackett-Burman test was designed to identify and select the parameters that have a significant effect on the angle of repose. The range of values of the significant parameters was then optimized using the steepest climb test. The Box-Behnken test was then utilized to calibrate and obtain the optimal parameter combinations. Finally, a validation test of the angle of repose was conducted using the calibrated DEM parameters. The relative error between the simulation results and the test results was 1.54%. Then further straight shear tests were conducted to verify the accuracy and validity of the DEM parameters. The results show that the calibrated parameters can provide a reference for the selection of discrete element simulation parameters for lunar soil simulant and the design and optimization of drilling and excavation machinery for lunar exploration.