Abstract: In the context of the global warming and the "carbon peaking & carbon neutrality" strategy, it is necessary to develop and use wood-based materials as an alternative to traditional structural and functional materials as a means to reduce energy consumption and greenhouse gas emissions, as well as to increase global carbon storage as consequence. Such development and replacement are of great significance for the preservation of the natural environment and for the achievement of a sustainable development in human society. During the past few years, in order to develop and utilize abundant wooden resources and improve the macroscopic performance of traditional wood-based materials, many researchers have been successful in achieving multiscale structural design and control from the microscale to the macroscale in natural wood with a top-down "two-step modification" approach. By modifying wood-based materials in such a way, researchers successfully equipped wood with various excellent macroscopic properties such as high mechanical strength, thus opening up a new field for developing and designing environmentally friendly high-performance wood-based materials that are sustainable and green. On the basis of such a background, this paper presents a review of recent top-down multi-scale structural design strategies for wood-based materials. First of all, there was a brief introduction to the inherent hierarchical structure of natural wood. Then, at microscale, the mechanical behavior and mechanism dominated by cellulose in high-performance wood-based materials were discussed. Subsequently, different strategies for modifying and regulating wood microstructures and the corresponding obtained wood-based materials with different macroscopic properties were reviewed from the perspective of cell wall engineering. Finally, a brief review of the latest developments in functionalized use of wood-based materials was presented. At the end of this paper, a summary of the insufficiency of existing multiscale structural design and modification strategies of wood-based materials was concluded, and the corresponding research prospects were given as potential solutions.