Biomimetic scaffolds present the promising potential for bone regeneration. As a natural gel-like traditional food, tofu with porous architecture and proved biological safety indicated a good potential to be a natural scaffold and easy to be improved by surface modification. Hereon, we fabricated the tofu-based scaffolds and systematically explored the potential for bone tissue engineering. In addition, the collagen has been introduced by simple coating to further enhance the surface compatibility of the tofu-based scaffold in bone regeneration. The results showed that the tofu-based scaffolds possessed good porous structure and cytocompatibility. Notably, the tofu-based scaffolds could improve the expression of osteogenesis-related genes and proteins, leading to better bone regeneration after 2 months of implantation. All the results indicated that tofu would become an outstanding sustainable natural porous scaffold for bone regeneration with excellent bioactivities.