Abstract: In order to screen an optimal thermal protective agent for immunoglobulin G in bovine colostrum, the IgG was extracted from bovine colostrum. Based on single factor experiments, the response value was the retention rate of IgG activity, and the response factors were glycine, maltitol and inulin. Box–Behnken experimental design on three levels and three variables was used for optimization of IgG thermal protectant. The structure of IgG was characterized by Fourier transform infrared Spectroscopy and endogenous fluorescence spectroscopy. The results showed that the best formula of IgG thermal protection agent was: Glycine 0.48%, inulin 14.98%, and maltitol 12.50%. Under these conditions, the IgG activity retention rate at 75 ℃ for 5 min was 36.59%, indicating that the response surface model had high accuracy and the optimized thermal protectant formula had practical application significance. The results of Fourier transform infrared spectrum and endogenous fluorescence spectrum analysis showed that compared with bovine colostrum IgG without compound heat protectant, the β-fold content decreased significantly (P<0.05), the irregular curl content decreased significantly (P<0.05), and the secondary conformation showed a more orderly state. The fluorescence intensity decreased, and IgG molecules piled up more tightly. The results showed that the structural stability of IgG in bovine colostrum was improved after adding compound heat protection agent. This research explored a new type of bovine colostrum IgG heat protectant formula, which would provide a reference for the further development and utilization of f functional foods from bovine colostrums.