Jinqi Jiangtang tablet (JQJTT), a traditional Chinese herbal medicine for treating diabetes, consists of Coptis chinensis, Astragalus membranaceus, and Lonicera japonica. In this study, we developed a method using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-MS) to analyze 21 compounds in JQJTT, belonging to five different types. Separation was performed on a C-18 column (150x4.6mm, 5 mu m), and the mobile phase for the gradient elution consisted of 2mM ammonium acetate and 0.1% acetic acid as an aqueous phase and acetonitrile as an organic phase. The method showed good linearity (r>0.9954). The relative standard deviation (RSD) values for the intra- and inter-day precision were less than 4.98% and 4.93%, respectively. The recovery at three concentration levels ranged from 90.15 to 109.90%, with RSD below 4.69%. Sample solutions were proven to be stable for more than 24h at 4 degrees C (RSD<4.87%). The novel method was successfully applied to systematic quality evaluation of JQJTT based on the quantification of the 21 compounds.