In recent years, TPMS lattice structures have attracted extensive attention from scholars around the world. In the practical applications, lattice structures usually should be optimally designed to meet the requirements of both lightweight and load-bearing capacity. Currently, optimal designs for TPMS lattice structures are limited to density gradient and the influence of loading directions on their mechanical properties has not been considered comprehensively. To this end, the anisotropic characteristics of TPMS lattice structures were investigated firstly. Their equivalent elastic matrixes were calculated based on the homogenization method, then their three-dimensional Young’s modulus diagrams were plotted by Matlab. The results showed that different types of TPMS lattice structures present different anisotropy characteristics. For instance, the strength of I-WP structure is higher in the axial direction [100] and weaker in the diagonal direction [111] while it is opposite for the Primitive structure. Subsequently, an optimization design method combining density gradient with hybridization was proposed by considering the density distribution and the principal stress directions. The optimization process was as follows: Firstly, a cantilever beam structure was topology optimized and the obtained density cloud was mapped to relative density distribution of the lattice structure. Then, based on the anisotropic characteristics of the TPMS lattice structures, I-WP and Primitive lattice cells were selected respectively to fill the cantilever beam according to the principal stress directions in order that the principal stress directions were located in the directions where the mechanical properties of the lattice cells are strong. After the TPMS lattice cells of different types were reasonably distributed, they were smoothly connected by an activation function. Finally, the relative density and lattice cell type distributions were combined to design a density graded hybrid lattice structure. The load-bearing performances of lattice structures before and after optimization designs were compared by finite element analysis. The results showed that the stiffness of density gradient I-WP and Primitive lattice structures are obviously improved compared with the uniform structures. And the stiffness of the graded hybrid lattice structure is highest, which is 4.63% and 33.63% higher than the density gradient I-WP and Primitive lattice structures respectively, demonstrating that hybridization design by reasonable distribution of different lattice cells according to the principal stress directions can further improve the overall stiffness. The established optimization method combining density gradient with hybridization for TPMS lattice structures provides a guidance for their applications in lightweight designs.