Abstract Construction of sustainable high-performance structural materials is a core part of the key global sustainability goal. Many efforts have been made in this field; however, challenges remain in terms of lowering costs by using all-green basic building blocks and improving mechanical properties to meet the demand of practical applications. Here, we report a robust and efficient bottom-up strategy with micro/nanoscale structure design to regenerate an isotropic wood from natural wood particles as a high-performance sustainable structural material. Regenerated isotropic wood (RGI-wood) exceeds the limitations of the anisotropic and inconsistent mechanical properties of natural wood, having isotropic flexural strength of ∼170 MPa and flexural modulus of ∼10 GPa. RGI-wood also shows superior water resistance and fire retardancy properties to natural pine wood. Mass production of large sized RGI-wood and functional RGI-wood nanocomposites can also be achieved.