Rationale: Erigeron breviscapus （EB）and Erigeron multiradiatus (EM) are the two species of the genus Erigeron (Asteraceae) with extremely close genetic relationships. They were used as the same “meiduoluomi” for the treatment of plague and epidemics in traditional Tibetan medicine. But in traditional Chinese medicine, only EB is used for treatment of cerebrovascular obstruction, hemiplegia due to stroke, coronary artery obstruction, chest congestion, angina pectoris. These two Erigeron species show different effects in different traditional medicines system. Therefore, analyzing the chemical compositions of two species will not only enhance comprehension of their medicinal properties, but also foster the advancement and exploration of novel applications. However, to date, there has been no comprehensive and detailed investigation comparing the constituents of EB and EM. Methods: A methodology for rapid identification of chemical profiles from two Erigeron species was devised through the integration of UHPLC-QTOF-MS/MS and multivariate statistical analysis. Additionally, a UHPLC-PDA method was established to precisely quantify of 11 components. Results: A total of 58 constituents comprising flavonoids, phenolics acids, saponin and long chain fatty acids were elucidated. Thirteen compounds were identified as potential differentiators in chemical profiles among the two Erigeron species. For quantitative assessment, 11 bioactive compounds were simultaneously quantified across 49 batches of Erigeron species samples utilizing UHPLC-PAD with wavelengths of 325 nm, 254 nm, and 266 nm. The method demonstrated excellent precision, linearity, accuracy, repeatability, stability, and recovery. Conclusions: The findings from this study will serve as a reference for quality control, functional activity exploration, and improved clinical application based on the ingredient profiles of the two species. Furthermore, this inaugural investigation into the ingredient profiles of these two species will enhance the potential and optimal utilization of both EB and EM resources.