Well‐designed cryoprotectants are crucial for successful probiotic application. In this study, based on literature analysis, characteristics and economic analysis of cryoprotectants, the sucrose (8.2%)–skim milk (8.0%)–inulin (8.2%) combination was proposed and optimised to enhance freeze‐drying resistance of probiotics. Survival, viable cell counts and inactivation rate during storage at 4°C of Lactiplantibacillus plantarum grx16 protected by the combination was 94.9%, 1.89 × 1011 cfu/g and 0.0116. The optimised sucrose–skim milk–polymer prebiotics combination could also effectively protect several other probiotics, with the survival rate being 89.2–95.6%. These results will aid in the rational development of synergistic cryoprotectant formulations for probiotics. [ABSTRACT FROM AUTHOR]