Danshen is one of the most frequently used traditional Chinese herbs owing to its remarkable and reliable therapeutic effects. Phenolic acids and diterpenoids have proved to be the bioactive substance groups. In order to fully profile its chemical compositions and explore new potential bioactive compounds, a comprehensive two-dimensional liquid chromatography system coupled to DAD detector and hybrid linear ion trap (LTQ) Orbitrap mass spectrometry (LC×LC-DAD-ESI/HRMS/MS) was set up in this study based on the column combination of Hypersil gold CN (150mm×1mm, 3μm) and Accucore C18 (50mm×4.6mm, 2.6μm). Using the optimal segment gradient program, phenolic acids and diterpenoids were separated into two independent groups and a total of 328 peaks were successfully detected on the contour plot of Danshen. By means of the accurate mass and reliable MS data, 102 compounds were identified or tentatively identified and 7 of them were discovered from Danshen for the first time. Moreover, the LC×LC-DAD system was validated for the quantitative analysis of 14 bioactive analytes using the contour plot, exhibiting satisfactory linearity (r≥0.9976) and high precision for both peak locating (≤1.07%) and peak volume calculating (0.34%-4.11%). The established method could afford powerful separation capability, reliable identification data and accurate quantitative results, which is very suitable for analysis of complex herbal samples.