Abstract: The preparation process for tilapia scale collagen peptide calcium chelate was optimized using response surface methodology, and a mathematical model was established to describe peptide calcium chelate ratio as a function of time, mass ratio of peptide to calcium chloride, temperature and pH. The optimal preparation parameters obtained were as follows:time 39min, mass ratio of peptide to calcium chloride 3.3∶1, temperature 61℃ and pH7.2. Under these conditions, the experimental value was 65.01%, which was no significant difference with the predicted value ( 65. 05 %) . Infrared spectroscopy showed that tilapia scale collagen peptide calcium chelate was formed. These experimental results provided a theoretical basis for the development of new calcium preparations and the high-value utilization of fish scales.