Particle mixing is a crucial operation in various industrial production processes. However, phenomena like segregation or local accumulation can arise, especially when particles differ in properties like radius and density. Numerical simulation of particles using Discrete Element Method (DEM) allows for the manipulation of control variables in batches, generating a large amount of data and facilitating quantitative research. In this study, the mixing behaviors of binary particles in rotating drums are systematically investigated. The DEM model is first validated with experimental data and then rotating drums with varying obstacles, rotation speeds, particle radii, and densities are simulated. Moreover, a Gaussian process-based optimization is conducted by correlating Lacey mixing index (MI) and parameterized shape of obstacle to find the optimized mixing condition. Experimental validations are further performed on the optimized condition to verify the design. It is shown that this integrated approach holds significant potential for enhancing the efficiency, effectiveness of industrial mixing processes and the consideration of energy consumption when balancing the mixing efficiency and optimal rotating speed.