Abstract: Objective: To explore the protective effect of Phallus impudicus L. extract on intestinal and liver structure and function damage induced by NCDC in mice. Methods: Firstly, the ultrasonic-assisted extraction was carried out, the ratio of material to liquid, ultrasonic time, ultrasonic power and extraction temperature were selected for single factor experiment, the content of polysaccharides and polyphenols, DPPH and hydroxyl radical scavenging rate and ferrous ion chelating rate were used as the evaluation indexes to analyze the four process conditions by entropy weight method. Subsequently, 40 of 8-week-old C57BL/6 male mice were randomly divided into 5 groups: Control group (ND), Model group (MG, 0.05 g/kg/d NCDC exposure), low/medium/high dose intervention group (LDPI/MDPI/HDPI, 10/20/30 g/kg/d intragastric administration of Phallus impudicus L. extract, 0.05 g/kg/d NCDC exposure). At the end of the experiment, pathological analyses of the small intestine and liver were performed, and serum liver function indicators and oxidative stress indicators in intestinal and liver tissues were determined. Results: The optimum ultrasonic-assisted extraction process parameters for Phallus impudicus L. were 1:30 solid-liquid ratio, 180 W ultrasonic power, 50 min ultrasonic time and 70 ℃ extraction temperature. The pathological results showed that compared with the model group, the intestinal and liver structural damage of the mice in the Phallus impudicus L. extract intervention groups was improved to varying degrees. In the low, medium and high dose groups, the swelling degree of villi was alleviated, the number and length of villi were increased, the depth of crypts was increased, the degree of diffuse vacuolar degeneration and punctate necrosis of hepatocytes was decreased, and the morphology and structure of intestinal and liver tissues were more complete. the therapeutic effect on the mice in the medium-dose and high-dose groups was significant (P<0.05), and the medium-dose group had the best effect. Physicochemical results showed that compared with the model group, the contents of serum alanine aminotransferase (ALT) (P<0.05) and aspartate aminotransferase (AST) (P<0.001) were significantly decreased in the low, medium and high-dose intervention groups. The extract of Phallus impudicus L. could also significantly up-regulate the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in intestine and liver, and down-regulate the level of malondialdehyde (MDA), especially in the middle-dose group, and the protective effect on intestinal oxidative damage was more prominent than that on liver. Conclusion: The comprehensive evaluation of entropy weight method could be effectively used to determine the optimal extraction conditions of edible fungi, and the obtained extract of Phallus impudicus L. had a good protective effect on intestinal and liver injury induced by disinfection by-product NCDC in mice.