This study developed a novel method of screening cryoprotectants used to improve the survivability of lyophilized Lactobacillus helveticus. To develop a liposome encapsulated beta-galactosidase (beta-gal) as a cell membrane model, the beta-gal liposome was characterized in terms of mean size, poly dispersity index, zeta potential, along with transmission electron microscopy. 800 W of ultrasonic power and 10 min of sonication time were the optimal experimental conditions to obtain the desirable beta-gal liposome. Subsequently, different cryoprotectants were mixed with the beta-gal liposome during freeze-drying. After freeze-drying, liposomes were hydrolized, and the protective effect of cryoprotectants was assessed as the release rate of encapsulated beta-gal. The lowest release rate of beta-gal was obtained using 10 mg/100 ml trehalose and 0.2 mg/100 ml hyaluronic acid.