Real meat and plant-based meat analogues have different in vitro protein digestibility properties. This study aims to further explore their in vivo digestion and absorption and their effects on the gastrointestinal digestive function of mice. Compared with the real pork and beef, plant-based meat analogues significantly reduced the number of gastric parietal cells, the levels of gastrin/CCKBR, acetylcholine/AchR, Ca2+, CAMK II, PKC, and PKA, the activity of H+, K+-ATPase, and pepsin, the duodenal villus height, and the ratio of villus height to crypt depth and downregulated the expression of most nitrogen nutrient sensors. Peptidomics revealed that plant-based meat analogues released fewer peptides during in vivo digestion and increased the host- and microbial-derived peptides. Moreover, the real beef showed better absorption properties. These results suggested that plant-based meat analogues weaken gastrointestinal digestive function of mice, and their digestion and absorption performance in vivo is not as good as the real meat.