Abstract: In this study, a novel polysaccharide liposome was prepared using garlic polysaccharides, soybean lecithin and cholesterol and structurally characterized. The optimal preparation conditions of garlic polysaccharide liposomes were determined by single-factor and response surface tests using the film-material ratio, lipid-drug ratio and ultrasonic time as factors and the encapsulation efficiency as response values. The obtained liposomes were characterized in terms of micromorphology, particle size, UV spectrum, IR spectrum and stability. The results showed that the optimal preparation conditions of garlic polysaccharide liposomes were as follows: Film-material ratio of 4:1, lipid-drug ratio of 24:1, ultrasonic time of 14 min, with the maximum encapsulation efficiency of 61.00%±0.73%. The obtained liposomes appeared as spherical vesicles with uniform dispersion and good stability. Their particle size, polymer dispersity index and zeta potential were 213.50±1.85 nm, 0.187±0.005 and −21.07±1.27 mV, respectively. UV and IR spectra confirmed that garlic polysaccharides were successfully encapsulated into the lipid material through electrostatic interactions, without the formation of new chemical bonds. After 28 days of storage at 4 ℃, the particle size of garlic polysaccharide liposomes increased from 211.13±0.54 nm to 225.70±0.65 nm, the PDI increased from 0.187±0.003 to 0.236±0.001, and the encapsulation efficiency decreased from 60.96%±0.32% to 56.97%±0.74%, exhibiting a relative stability. Therefore, the garlic polysaccharide liposomes prepared in this study had high encapsulation efficiency, small particle size, good dispersion and high stability, which could provide a reference for the development of garlic polysaccharide derivatives.