Origami-based multistable metamaterials have been recognized as a promising platform for diverse applications due to their exceptional mechanical properties. However, the current state of the art in designing origami metamaterials is mostly ad-hoc and narrowly focused on a particular mechanical property. In other words, there is a lack of basic research on deriving generic and systematic methodologies for the design, configuration tuning, and property programming of origami metamaterials, to explore their achievable ranges of mechanical properties comprehensively from the perspective of mechanics. In this work, a mathematically rigorous strategy for synthesizing and reconfiguring multistable origami metamaterials based on two basic modules is put forward, and a systematic approach to analyze and program the material properties is proposed. More specifically, by programming the binary design array of module arrangement and by mathematically expressing the connection constraints, a number of multistable origami cells with exceptional shape reconfigurability are generated. Building upon this, the fundamental mechanics properties, including the multistability, global stress-strain profiles, and tangent elastic moduli, are thoroughly investigated via examining the unit cell, i.e., the “infinitesimal element,” of the metamaterial. Considering the extreme cases of the unit cell architecture, boundaries of the material properties of the synthesized metamaterials at the stress-free configuration are derived, which are of vital importance for material selections and topological optimization. Moreover, due to the topologically different configurations, six categories of metamaterials with qualitatively different material densities and moduli programmability are revealed. In addition to the reprogrammable density and Young's modulus of conventional Miura origami metamaterial, more intriguing properties, such as reprogrammable shearing modulus, locking effect, and inner reconfiguration without modulus change, are discovered for the first time. A prototype made of dual-material 3D printing is created to experimentally evaluate and verify the effectiveness of the analysis method and the characterized material properties. Overall, this work provides a rigorous tool for designing multistable origami metamaterials and an effective strategy for characterizing their fundamental mechanical properties, which will greatly enhance the systematization of creating origami metamaterials.