In this paper, a typical negative Poisson's ratio lattice structure was studied and several diagonally reinforced 3D lattice structures were designed and analysed using the finite element method. On this basis, the fatigue life of the unreinforced and reinforced structures was calculated using SIMULIA Fe-safe software. Meanwhile, the fatigue failure process of the lattice structure was systematically simulated and quantitatively analysed by combining the multiaxial fatigue damage model. Results show that the enhancement design from the cell structure can provide an anti-diagonal shear enhancement effect. The structure A, B, and C can decrease the maximum von Mises stress by 95.8, 97.1, and 94.66%, and increase the compressibility by 80, 56, and 127%, respectively. The structure A enhancement yields the best overall performance in terms of structural stress, compressibility, and negative Poisson's ratio properties enhancement. Compared with the unreinforced structure, the lifetime distribution of the structure A reinforced structure changes in both position and level. The overall lifetime has been improved from 102.813 of the unreinforced structure to 107 of the reinforced structure. Quantitative calculation of the fatigue damage is consistent with the fatigue life prediction results, which further validate the effectiveness of the diagonal enhancement method and the enhancement structure of the negative Poisson's ratio lattice structure.