Astragalus ponticus Pall. species was investigated for its antiproliferative effects on HeLa cells. Two new chalcones (B5 and B8) along with eight known compounds (B1, B2, B3, B6, B7, B10, B14 and B15) were isolated by following bioactivity guided isolation methods. In addition, from non-active fraction, three cycloartane glycosides (B11, B12 and B13) were isolated. Molecular structures of these isolated compounds were revealed by using spectroscopic methods like MS, 1D and 2D NMR and a single crystal X-ray diffraction analysis. New compounds B5 and B8 showed the highest antiproliferative activities against HeLa cells (IC50 values of 36.6 and 20.6 µM, respectively) while the rest showed high and low activities. Non-endemic species attract relatively low attention from the scientific community but this study demonstrates that valuable new compounds, which might be used as ingredients in medicinal preparations, can be obtained from these materials.