A novel environmentally friendly thermoplastic soy protein/polyester blend was successfully prepared by blending soy protein isolate (SPI) with poly(butylene succinate) (PBS). To improve the compatibility between SPI and PBS, the polyester was pretreated by introducing different amounts of urethane and isocyanate groups before blending. The blends containing pretreated PBS showed much finer phase structures because of good dispersion of polyester in protein. Consequently, the tensile strength and modulus of blends increased obviously. A lower glass transition temperature of protein in the blends than that of the pure SPI, which was caused by the improvement of the compatibility between two phases, was observed by dynamic mechanical analyzer (DMA). The hydrophobicity, water resistance, and moisture absorption at different humidities of the blends were modified significantly due to the incorporation of PBS.