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[Display omitted] • A high-performance soybean protein adhesive was developed using agricultural raw material as the main ingredient. • Mesoporous silica entrapped alpha-mangostin nanoparticles were hybridized in situ. • The hybrid invigorated soybean protein adhesive via dynamic covalent and sacrificial hydrogen bonds. • The developed strategy enhanced the fabricated plywood's dry and wet shear strength by 66% and 206%, respectively. • The adhesive's insoluble fraction, thermal stability, and shelf-life remarkably improved. The production of value-added products from agricultural raw materials has been deemed a cutting-edge approach to attaining an uncontaminated geosphere globally. Thus, soybeans have recently attracted several wood-bonding capability studies due to their biobased, high-performance, and sustainable attributes. However, simultaneously achieving high-performance, mechanical, and anti-mildew properties in soybean protein (SBP) adhesive remains an enormous quest. Herein, an organic–inorganic strategy is reported to formulate SBP adhesive via adipic acid hydrazide strengthened α-mangostin (Sα-M) entrapped by mesoporous silica nanoparticles (MSN), yielding a highly biocompatible dense network (MSN/Sα-M). Afterward, the MSN/Sα-M was incorporated into SBP molecular chains through the enhanced dynamic covalent conjugation and intermolecular sacrificial hydrogen bonds to form SBP@MSN/Sα-M adhesive. Consequently, the multiple synergistic interactions resulted in tough adhesive layers, exhibiting high wood-bonding strength of 2.59 and 1.50 MPa at dry and wet conditions, increasing 66% and 206%, respectively. The SBP@MSN/Sα-M adhesive also offers excellent anti-mildew properties, with an extended wood bonding capability beyond 20 days of storage. This unique, versatile, and sustainable strategy provides new headway for developing bio-based wood adhesives from agricultural raw materials. [ABSTRACT FROM AUTHOR]