Bio-based adhesives show enormous potential to replace petroleum-based adhesives that release toxic formaldehyde, but they typically encounter limitations such as poor waterproof bonding strength and a propensity for mildew growth. In this work, a one-pot method was employed to synthesize the SOTS/CS/CNF adhesive, with acid-catalyzed sucrose solution (SS), oxidized tannin (OT), soybean protein isolate (SPI), chitosan (CS), and cellulose nanofibers (CNF) serving as raw materials. The results indicate that the SOTS/CS/CNF adhesive forms a dense dual cross-linked network through covalent cross-linking structures and non-covalent structure (primarily hydrogen bonding), exhibits excellent water resistance. The dry and wet shear strength of the prepared plywood reached 2.65 and 2.17 MPa, respectively, far exceeding the minimum value of 0.7 MPa specified in the Chinese national standard for plywood (GB/T 9846-2015). By incorporating condensed tannins and chitosan, the SOTS/CS/CNF adhesive demonstrates excellent mildew resistance, which effectively extends its storage duration. This study offers a promising and practical strategy for developing green, water-resistant bio-based adhesives, which show great potential as sustainable alternatives to conventional wood adhesives.