The Orowan-Petch relation is a famous model to describe the strength of polycrystalline ceramics covering a wide range of grain sizes. However, it becomes difficult to explain the strength trend when the grain size decreases to the sub-microscale or nanoscale. This is because some microstructural parameters (such as grain size, grain boundary fracture energy, and grain boundary defects) vary with different processing technologies, and their coupling effects on mechanical properties are still unclear. In this study, a finite element method (FEM) was applied to investigate the dependence of mechanical properties, such as strength and damage resistance, on the abovementioned microstructural parameters on example of alumina. The numerical results show that the grain boundary energy is weakly coupled with the grain size and grain boundary defects. The grain size and grain boundary are intercoupling, which affects mechanical properties. The mechanical properties could be improved by increasing the grain boundary fracture energy and decreasing the grain size and the grain boundary defect density.