Summary: A novel computational framework for designing metamaterials with negative Poisson’s ratio over a large strain range is presented in this work by combining the density-based topology optimization together with a mixed stress/deformation driven nonlinear homogenization method. A measure of Poisson’s ratio based on the macro deformations is proposed, which is further validated through direct numerical simulations. With the consistent optimization formulations based on nonlinear homogenization, auxetic metamaterial designs with respect to different loading orientations and with different unit cell domains are systematically explored. In addition, the extension to multimaterial auxetic metamaterial designs is also considered, and stable optimization formulations are presented to obtain discrete metamaterial topologies under finite strains. Various new auxetic designs are obtained based on the proposed framework. To validate the performance of optimized designs, a multiscale stability analysis is carried out using the Bloch analysis and rank-one convexity check. As demonstrated, short and/or long wavelength instabilities can occur during the loading process, leading to a change of periodicity of the microstructure, which can affect the performance of an optimized design.