The purpose of this study was to improve the performance of soy protein isolate (SPI) adhesives using a polyurethane elastomer. Triglycidylamine (TGA), SPI, thermoplastic polyurethane elastomer (TPU), and γ-(2,3-epoxypropoxy) propyltrimethoxysilane (KH-560) were used to develop a novel SPI-based adhesive. The residual rate, functional groups, thermal stability, and fracture surface micrographs of the cured adhesives were characterized. Three-ply plywood was fabricated, and the dry/wet shear strength was determined. The experimental results suggested that introducing 2% TGA improved the residual rate of the SPI/TGA adhesive by 4.1% because of the chemical cross-linking reaction between epoxy groups and protein molecules. Incorporating 7% TPU into the SPI/TGA adhesive, the residual rate of the adhesive increased by 5.2% and the dry/wet shear strength of plywood bonded by SPI/TGA/TPU adhesive increased by 10.7%/67.7%, respectively, compared with that of SPI/TGA adhesive. When using KH-560 and TPU together, the residual rate of the adhesive improved by 0.9% compared with that of SPI/TGA/TPU adhesive. The dry and wet shear strength of the plywood bonded by the SPI/TGA/TPU/KG-560 adhesive further increased by 23.2% and 23.6% respectively when compared with that of SPI/TGA/TPU adhesive. TPU physically combined with the SPI/TGA adhesive to form a interpenetration network and KH-560 acted as a bridge to connect TPU and SPI/TGA to form a joined crosslinking network, which improved the thermo stability/toughness of the adhesive and created a uniform ductile fracture section of the adhesive.