A novel strategy for predicting bioactive components in traditional Chinese medicines (TCM) using live cell extraction and high performance liquid chromatography–diode array detection–mass spectrometry (HPLC–DAD–MS) analysis was proposed. The hypothesis is that when cells are incubated together with the extract of TCM, the potential bioactive components in the TCM should selectively combine with the cells, and the relative concentrations of the cell-combining components in the suspension medium should decrease, while the cell-combining components would be detectable in the extract of denatured cells. The identities of the cell-combining components could be determined by HPLC–DAD–MS analysis. Using the proposed approach, the potential bioactive components of Danggui Buxue decoction, a commonly used TCM for anaemia, and its compositions, Radix Angelica Sinensis and Radix Astragli for endothelial cells, were investigated. Six compounds in the extract of Danggui Buxue decoction were detected as the components selectively combined with endothelial cells, among them two were contributed by Radix Angelica Sinensis, and four by Radix Astragli. The identities of four of the six potential bioactive compounds were elucidated as ononoside, calycosin, 3-butylphthalide and ligustilide by HPLC–DAD–MS analysis. The results indicate that the proposed approach may be applied to predict the bioactive candidates in TCM.