Abstract: This study aimed to investigate the osteo-inductive capacity of a fucoidan polysaccharide network derived from brown algae on human adipose-derived stem cells (HA-MSCs) for bone regeneration. The physiochemical properties of the scaffold including surface morphology, surface chemistry, hydrophilicity, mechanical stiffness, and porosity were thoroughly characterized. Both in vitro and in vivo measurements implied a superior cell viability, proliferation, adhesion, and osteo-inductive performance of obtained scaffolds compared to using specific osteogenic induction medium with increased irregular growth of calcium crystallites, which mimic the structure of natural bones. That scaffold was highly biocompatible and suitable for cell cultures. Various examinations, such as quantification of mineralization, alkaline phosphatase, gene expression, and immunocytochemical staining of pre-osteocyte and bone markers confirmed that HAD-MSCs differentiate into osteoblasts, even without an osteogenic induction medium. This study provides evidence for the positive relationship and synergistic effects between the physical properties of the decellularized seaweed scaffold and the chemical composition of fucoidan in promoting the osteogenic differentiation of HA-MSCs. Altogether, the natural matrices derived from brown seaweed offers a sustainable, cost-effective, non-toxic bioinspired scaffold and holds promise for future clinical applications in orthopedics.