Abstract: In order to further improve the utilization value of Perilla resources, this study used Perilla seed shell extract (PSHE) as raw material, through single factor experiments, the effects of silver nitrate concentration, extract concentration, ultrasonic power, ultrasonic temperature and ultrasonic time on the silver ion reduction rate of Perilla seed shell extract silver nanoparticles (PSHE@AgNPs) were investigated, response surface methodology (RSM) was used to optimize the ultrasonic-assisted preparation of PSHE@AgNPs, the structure and properties of PSHE@AgNPs were characterized by X-ray diffraction, fourier transform infrared spectroscopy, thermogravimetric analysis and transmission electron microscope. The results showed that the optimal PSHE@AgNPs preparation process involved a silver nitrate concentration 15 mmol/L, extract concentration 0.4 g/mL, ultrasonic power 480 W, ultrasonic temperature 80 ℃, and ultrasonic time 7 hours. Under these conditions, the silver ion reduction rate of PSHE@AgNPs reached an impressive 92.37%. X-ray diffraction analysis confirmed the presence of a face-centered cubic structure in PSHE@AgNPs. Fourier-transform infrared spectroscopy showed that there were plant chemical substances on the surface of PSHE@AgNPs, and phenolic compounds were involved in the synthesis of nano-silver. Thermal gravimetric analysis demonstrated the exceptional thermal stability of PSHE@AgNPs, with a major mass loss of 46.74% in the range of 276.7~420.3 ℃. Transmission electron microscopy displayed PSHE@AgNPs as highly dispersed near-spherical particles with an average particle size of 27.97 nm. These research findings would provide valuable theoretical guidance for the ultrasound-assisted green synthesis of PSHE@AgNPs with small particle size, superior dispersion, and remarkable thermal stability in a face-centered cubic structure. Furthermore, these results contribute to advancing the application of PSHE@AgNPs in the fields of biomaterials and medicine.