The discrete element method (DEM) has demonstrated significant advantages in modelling feed-tool interaction. The selection of an appropriate contact model and its parameter calibration is crucial for developing effective DEM simulations. A DEM model of feed powder was developed to forecast powder compression and densification in feed pelleting by using the Edinburgh elasto-plastic adhesion contact model. Firstly, a calibration method of DEM parameters based on the Plackett–Burman (PB) and the central composite (CC) test was proposed to enhance calibration efficiency. Both experimentally and through DEM simulation of the uniaxial confined compression experiments, powder repose angle experiments, and powder static friction angle experiments were used to calibrate the DEM parameters. Extract the DEM parameters that have a significant impact on feed pelleting through PB testing. Then, the effects of these parameters on response were analysed using CC testing, and ascertain their optimal values. Finally, the single-hole open compression experiment and feed pelleting experiment were used to evaluate the accuracy of the parameters. The results show that the average relative error between the predicted ultimate compressive force in the open compression experiment and the measured value is 8.16%, and that of the torque of the pellet mill is 2.10%. Thus, it was shown that the modelling and calibration method can effectively predict the compression and densification of powder in the feed pelleting.