Gandi capsule (GDC) has been used clinically for years for treatment of vascular lesions caused by diabetes. However, its comprehensive ingredients, especially those that can be absorbed, remain unclear. In this study, we developed a simple and fast ultra-high performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC–Q-TOFMS) method to identify the ingredients of GDC extract, as well as those that can permeate the Caco-2 monolayer cell model. Firstly, 52 components were rapidly identified in GDC extract. Then, a total of 17 components were able to pass across Caco-2 cells from the apical side to the basolateral side with the apparent permeability coefficients ( P app ) > 1.0 × 10 −5 cm/s, which indicate good intestinal permeability and bioavailability. Furthermore, 14 of the 17 penetrative components were definitely detected and identified in rat plasma. These results confirmed that the combination of Caco-2 monolayer cell absorption model and UHPLC–Q-TOFMS is suitable for fast screening of the ingredients entering the blood circulation. Our results will serve as a foundation for further evaluation of the pharmacological efficacy of GDC in the clinical treatment of diabetic vascular disease. Graphical abstract