Understanding the biomechanical properties of safflowers is essential for appropriately designing harvesting machinery and optimizing the harvesting process. Safflower is a flexible crop that lacks a basis for relevant simulation parameters, which causes difficulties in designing harvesting machinery. In this study, a calibration method for safflowers was proposed. First, a discrete element model was established by measuring the intrinsic parameters of a safflower, such as its geometric parameters, density, Poisson's ratio, and modulus of elasticity. Second, the contact and bonding parameters were calibrated using a combination of physical and simulation tests. In the contact parameter tests, the Hertz-Mindlin (no-slip) model was implemented for the stacking angle tests conducted regarding the safflower filament. A regular two-level factorial design was used to determine the important factors and perform the steepest climb test. Moreover, the Box-Behnken design was adopted to obtain the optimal contact parameters. In the bonding parameter tests, the Hertz-Mindlin model with bonding contact was applied for the safflower shear simulation tests; moreover, the optimum bonding parameters were obtained through the central composite design test. The results demonstrated that the relative errors between the simulated and measured stacking angles and maximum shear were 3.19% and 5.29%, respectively. As a result, the safflower simulation parameters were accurately calibrated, providing a reference for appropriately setting the simulation parameters and designing key mechanical components.