Objective To explore the effect of Qiwei Baizhu Powder on the activities of intestinal β-D-glucosidase and β-D-glucuronidase in mice with antibiotic-associated diarrhea(AAD), and to explain the mechanism of Qiwei Baizhu Powder in treating AAD from the perspective of intestinal glycoside hydrolase. Methods AAD mice model was constructed using a mixed antibiotic solution and treated with gavage Qiwei Baizhu Powder decoction. Specimens of small intestine contents (SC), small intestine mucosa (SM), colon contents (CC), and colon mucosa (CM) from mice were collected after modeling and treatment respectively to detect intestinal glycoside hydrolase activity. Blood and liver specimens were taken to detect succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), oxi-dative stress indicator malondialdehyde(MDA), inflammatory factor interleukin-17 (IL-17), and lipopolysaccharide (LPS). Results The activities of β-D-glucosidase and β-D-glucuronidase decreased significantly in SC, SM and CC in AAD mice (all P < 0.05), while increased significantly in CM (all P < 0.05). After treatment with Qiwei Baizhu Powder, glycoside hydrolase activity in each intestinal segment of mice in the treatment group was higher than that in the normal group and the natural recovery group. Compared to the natural recovery group, blood MDA, LDH, IL-17 and LPS decreased in the treatment group, while SDH increased. Conclusion Glycoside hydrolase activities in mice SC, SM, and CC decreases with antibiotics, while increases in CM. Qiwei Baizhu Powder can effectively regulate the activities of intestinal glycoside hydrolase, energy metabolism, oxidative stress, and inflammatory factors in AAD mice, restore their metabolic ability, improve the intestinal environment of mice, and treat diarrhea.