Abstract: The study aimed to determine the in vitro digestive properties of barbary wolfberry multigrain meal replacement powders with a low glycemic index (GI). The basic components, water absorption and swelling rate, starch components, starch hydrolysis rate, and estimated glycemic index (eGI) of each raw material powder and meal replacement powder were measured. The changes in protein hydrolysis rate, total phenolic content, flavonoid content and antioxidant activity in each raw material powder and meal replacement powder were comparatively analyzed by in vitro simulation of gastrointestinal digestive methods. The results showed that the contents of fat and crude fiber in the meal replacement powder was lower than the raw material powders. The water absorption rate of each raw material powder and meal replacement powder at a high temperature was approximately two times of that at room temperature, among which the meal replacement powder had the lowest water absorption rate (0.27%±0.05% at room temperature and 0.59%±0.05% at a high temperature). The rapidly digestion starch content (40.4%±0.003%) and eGI value (23.4) of the meal replacement powder were the lowest among all the ingredient powders, while the slowly digestion starch and resistant starch contents were both relatively high. In the in vitro simulated gastrointestinal digestion experiment, the protein hydrolysis rate of each raw material powder and meal replacement powder gradually increased and the hydrolysis was mainly in the stomach, in which the protein hydrolysis rate of the meal replacement powder was relatively high. The total phenol content tended to increase during gastrointestinal digestion, and the meal replacement powder reached the highest content at the end of digestion (5.46 and 7.26 mg/g, respectively). The flavonoid content increased significantly during simulated gastric digestion and decreased in simulated intestinal digestion. DPPH and ABTS⁺ radical scavenging rates increased significantly with time during simulated gastric digestion, whereas they tended to increase and then decrease with time during simulated intestinal digestion, but the overall magnitude of the changes was relatively low. In summary, barbary wolfberry multigrain meal replacement powder is suitable as a low GI ingredient or product and has good antioxidant capacity, which is of significance in guiding the development of miscellaneous grain products.