The target of this research is to investigate the anticancer potentiality of the Convolvulus spicatus and Astragalus vogelii. This study concentrated on the molecular pathways including apoptosis and cell cycle arrest of the anticancer cytotoxic effect. Methanol extract of each plant was prepared and utilized. Human Colon (Caco-2) and lung (A549) cancer cell lines were used. Antioxidant power and some phytochemical contents of every extract were measured. The cytotoxic activity of each extract was assessed as well as apoptosis induction. The mRNA level of Bax and Bcl2 apoptosis regulatory genes was detected. The obtained data showed that, the C. Spicatus methanolic extract had the highest total phenolic content, total flavonoid content and antioxidant power in comparison with A. vogelii. Both plants revealed cytotoxic effect on Caco-2 and A549 with different IC50 values and antioxidant power. C. spicatus and A. vogelii extracts exerted clear cytotoxic activity against human Caco-2 and A549 cells, foremost by means of cell cycle arresting at the G2/M phase associated with the pre G1 apoptosis induction. An apparent increase in the mRNA level of Bax and a concomitant decrease in Bcl-2 mRNA level were observed in the Caco-2 and A549 cells treated with C. spicatus and A. vogelii respectively. This study concluded that, Convolvulus spicatus and Astragalus vogelii induced apoptotic cell death and suggests that Convolvulus spicatus and Astragalus vogelii possibly can be utilized as new sources of an apoptosis-inducing anticancer agent for colon and lung cancer treatment with further detailed studies.