Abstract: CBD-NLC was prepared by film ultrasonic method with soybean phospholipid and cholesterol as solid esters. The effects of mass ratio of phospholipid to cholesterol, mass concentration of CBD broad-spectrum oil, pH value of buffer solution, rotary evaporation temperature and ultrasonic time on the encapsulation efficiency of CBD-NLC were analyzed by single factor experiment, The four factors which have great influence on the preparation of CBD-NLC were optimized by response surface test. The results showed that the optimum preparation conditions were as follows: the mass ratio of phospholipid to cholesterol was 3.4:1, the mass concentration of CBD broad-spectrum oil was 9.5%, the pH of buffer solution was 7.3, the rotary evaporation temperature was 39.1 ℃, and the ultrasonic time was 30 min. The results showed that the encapsulation efficiency of CBD-NLC was (91.3%±0.37%), the particle size was (94.0±0.4) nm, the PDI was (0.213±0.017), the zeta potential was (−45.0±0.8) mV. The color of CBD-NLC suspension is light yellow, with good dispersion uniformity and stability, which lays a foundation for the further development and application of CBD broad-spectrum oil.