Sea buckthorn has good food medicine homology characteristics and is widely used in food processing and the development of functional foods. Lacticaseibacillus paracasei SMN-LBK (SMN-LBK) has been proven to have excellent probiotic properties. Preparing SMN-LBK-sea buckthorn mixture is a new strategy for jointly developing functional foods containing probiotics and food and medicine homologous raw materials. In this study, we screened the types of freeze-drying protectants for composite probiotic powder and optimized their freeze-drying process. The formulation of cryoprotectants was evaluated and optimized by response surface methodology using survival rate as an evaluation index. The results showed that the optimal formula was 10% sea buckthorn, 10% trehalose, 15% sucrose, 16% skim milk powder, and 4% sorbitol. On this basis, further optimizing the process conditions of freeze-drying was carried out. We found that the ratio of bacteria to the composite protective agent was 1:1, the thickness of the bacterial solution was 0.4 cm, and the pre-equilibration time was 30 min, and this resulted in the highest survival rate (88% ± 0.8%) of SMN-LBK. Additionally, the effects of freeze-drying on the antioxidant and enzyme activities of the mixture were evaluated. The DPPH radical scavenging rate was up to 72% at a concentration of 5 mg/mL, implying that the mixture had good antioxidant properties. The enzyme activities of LDH, HK, and ATPase of the mixture were significantly higher compared with those of the absence of protective agents, while PK showed no significant change, suggesting that PK may not be the key enzyme affecting the lyophilized activity of the mixture. This provides a theoretical basis for the development of food medicine homologous composite probiotic products.