Abstract: The aim of this study was to investigate the effect of Jujubae Fructus (JF) on the gastrointestinal toxicity and diuretic effect of Crotonis Semen Pulveratum (CT). Forty-eight mice were randomly divided into the control group, low dose of CT group (0.039 g·kg^-1·d^-1, CTL), high dose of CT group (0.078 g·kg^-1·d^-1, CTH), JF group (9.75 g·kg^-1·d^-1), low dose of CT combined with JF group (CT 0.039 g·kg^-1·d^-1 and JF 9.75 g·kg^-1·d^-1, JFCTL), high dose of CT combined with JF group (CT 0.078 g·kg^-1·d^-1 and JF 9.75 g·kg^-1·d^-1, JFCTH). On the 9^th day of oral administration, the urine output of all mice was measured. After oral administration for ten days, fresh fecal samples were collected, and the 16S rDNA sequencing method was used to study the changes of intestinal bacteria when CT used alone and combined with JF. All experimental protocols were approved by the Animal Ethics Committee of Nanjing University of Chinese Medicine. The results showed that JF slowed down the rapid diuretic effect of CT, and significantly increased serum interleukin-2 (IL-2), interleukin-6 (IL-6), gastrin (GAS), somatostatin (SS). JF also reduced small intestine injury and improved the disorder of intestinal flora caused by CT. Low dose CT combined with JF significantly decreased the relative abundance of Sphingomonas and Oscillospira. The level of Bilophila was decreased after the combined application of high dose CT and JF. The results suggest that JF exhibited a tendency to reduce the toxicity of CT in the aspects of serum immune index, intestinal movement, intestinal damage, and intestinal microflora structure. In addition, the JF could also slow down the rapid diuretic effect of CT, behaving a tendency to reduce the clinical effect of CT.