Hesperidin (HPD) and hesperetin (HPT), as a kind of flavonone compounds, are abundant in citrus fruits with various pharmacological effects. HPD and HPT are not always consistent in some biological activities, even if they have the same skeletal structure. The aim of this study was to screen and identify HPT and HPD metabolites in rats using UHPLC-LTQ-Orbitrap MS n , compare the possible metabolism and provide the research basis for further understanding the similarities and differences in pharmacodynamics and pharmacokinetics of HPT and HPD. A total of 17 and 52 metabolites were identified in rats after oral administration of HPT or HPD, respectively. Three of HPT and HPD metabolites, glucuronidation, sulfation and diglucuronidation of HPT, were the same and could be the active components for the same pharmacodynamic action of them. We could find prototype in the urine sample of HPD group, but no prototypes in any samples of HPT group. There were hardly any general phase I metabolites of HPT, while 33 phase I metabolites of HPD could be identified. These data suggested that the poorer bioavailability of HPD compared with HPT.