Quality control of Traditional Chinese Medicinal formula is difficult because of the complexity of the matrix and differences in the formulations of the various specific components. In this study, a combination of liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) analysis method was successfully developed to identify the main flavonoids and saponins from Gui-zhi- tang (GZT). GZT, comprising five herbal medicines (Cinnamomum cassia, Paeonia lactiflora, Zingiber officinale, Glycyrrhiza glabra, Ziziphus jujube), is an important herbal remedy in Traditional Chinese Medicine. The chromatographic separation of GZT was performed on a C18 column with acetonitrile-water–formic acid as mobile phase. LC-ESI-MS/MS was used in a complementary manner to determine seven compounds of GZT. Furthermore, the ethanolic fraction of the GZT were using for LC-MS/MS analysis directly without any further complicated pretreatment. The study provides the chemical support for the chromatographic fingerprint technology and a basis for the quality control of GZT extracts and preparations.