Background Pomegranate peels have been widely used to treat diarrhea in China. The antidiarrheal activities of aqueous extracts of pomegranate peels have been evaluated. However, there have not been any bioactivity‐guided fractionation studies on the antidiarrheal effect to identify the bioactive components of the extract. Methods Bioactivity‐guided fractionation of an aqueous extract of pomegranate peels was performed using different solvents of increasing polarity, generating fractions dissolved in ethyl acetate, n‐butyl alcohol, and the residual fraction. The principal chemical composition of the active fraction was analyzed by HPLC/ESI‐MS. Key Results Fecal frequencies revealed that only the ethyl acetate fraction possessed significant antidiarrheal activity. Furthermore, administration of the ethyl acetate fraction at 100, 200, and 400 mg/kg significantly reduced gastrointestinal transit in charcoal meal tests in mice. It also significantly inhibited castor oil‐induced enteropooling compared to control animals. Histopathological analysis revealed that small intestine lesions of mice treated with the ethyl acetate fraction were alleviated compared to those in mice treated with castor oil. The ethyl acetate fraction was found to be composed mainly of punicalagin, corilagin, and ellagic acid, and a combination of these compounds could mediate the antidiarrheal activities. Conclusion and Inferences Our study describes the protective effects of pomegranate peels against castor oil‐induced diarrhea. The findings showed that the ethyl acetate fraction was the active fraction of pomegranate peels, of which punicalagin, corilagin, and ellagic acid were responsible for the antidiarrheal effect of aqueous extracts. The antidiarrheal activities of aqueous extracts of pomegranate peels have been evaluated. However, the effective ingredients of antidiarrheal activities need to be determined.( The ethyl acetate fraction was the active fraction of pomegranate peels, of which punicalagin, corilagin, and ellagic acid were responsible for the antidiarrheal effect of aqueous extracts. )Determination of effective ingredients is conductive to the application of pomegranate peels on diarrheal diseases.