This study aims to establish a multi-index quantification combined chemometrics and weighted TOPSIS model for comprehensive quality evaluation of Salviae Plebeiae Herba (SPH) from different producing areas. The contents of chlorogenic acid, caffeic acid, ferulic acid, nepetin, homoplantaginin, hispidulin, luteolin-7-O-glucopyranoside, apigenin, carnosol, oleanolic acid, Eleutheroside a and β-sitosterol in SPH were determined by HPLC-QAMS with rosmarinic acid and ursolic acid as internal reference substances, At the same time, the contents of alcohol-soluble extract, water-soluble extract and total ash were detected, and a multi-index quantification detection method for SPH was established. Principal component analysis, orthogonal partial least squares-discriminant analysis and other chemometric methods were used to analyze the data of multi-index quantification detection results, so as to realize the clustering of SPH from different producing areas and explore the main potential markers affecting the quality of SPH. At the same time, a weighted TOPSIS model was established to rank the quality of SPH samples from different producing areas. The experimental results showed that the 14 quantitative detection components had a good linear relationship in their respective mass concentration ranges (r> 0.999), the average recovery was 96.97%-100.1% (RSD< 2.0%), and the relative correction factor had good durability (RSD < 2.0%). The QAMS method can be used for simultaneous detection of 14 components in SPH. Eighteen batches of samples were clustered into 3 categories. Hispidulin, homoplantaginin, rosmarinic acid, nepetin, caffeic acid, carnosol and apigenin may be the main potential markers affecting the quality of SPH. The analysis results of the weighted TOPSIS method revealed that the closeness (J_b) for evaluating the quality of 18 batches of SPH ranged from 0.161 8 to 0.661 2, The weighted TOPSIS model could be used to sort the quality of SPH samples. The experimental results show that the multi-index quantification detection method established in this study is simple and accurate, and the combined chemometrics and weighted TOPSIS model can be used for the comprehensive quality evaluation of SPH from different producing areas.