Objective Bone tissue engineering scaffolds play a crucial role in the repair of bone defects. The size and performance requirements of scaffolds vary with the extents of the bone defects. Based on multi-objective optimization, a design method for Voronoi bionic porous scaffolds tailored to different extents of bone defects was proposed in this study. Method First, the effects of different variables on the mechanical and biological properties of scaffolds were investigated. Second, response surface models were established respectively for the design variables and performance indicators (including specific surface area, elastic modulus, yield strength, and permeability). Third, using a cubic scaffold with side length of 15 mm as an example (assuming a corresponding bone defect of the same dimension), multi-objective optimization of the scaffold was conducted using the non-dominated genetic algorithm-II algorithm, while considering the elastic modulus and permeability ranges of bone tissue as performance constraints. Results The degree of anisotropy in Voronoi scaffolds was influenced by the number of seed points, while the size and scaling factors of the scaffolds exclusively impacted the rod diameter and rod length. Using the design method of this study, the optimal scaffold with specific defect size satisfying mechanical and biological properties was obtained. The optimal scaffold under different strength requirements was obtained by adjusting the yield strength to change the utopia point. Conclusion In this study, a design method for Voronoi bionic porous scaffolds based on multi-objective optimization was proposed. This method can be applied to different extents of bone defects and provided a new approach to the personalized design of bone tissue engineering scaffolds.