Background: Catha edulis (Khat) is an evergreen shrub or small tree, traditionally used by various peoples of the Arabian Peninsula and Africa as an integral component of the socioeconomic traditions. It is believed that the psychostimulant nature and toxic nature of khat is primarily due to the presence of cathinone and cathine respectively. Studies have shown that khat chewing is closely associated with cardiac complications, especially myocardial infarction. Hence in this study, we exposed cathine-rich khat extract in a cardiomyoblast H9c2 (2-1) cell line to check the cell death mechanism. Materials and Methods: Extraction of Catha edulis leaves was done and the presence of cathine was confirmed with LC-MS-MS. The anti-proliferative activity was assayed using MTT and apoptosis detection by acridine orange/propidium iodide assay. The expression of Bcl-2 and Bax protein and caspase-3/7 expression were analyzed. The level of reactive oxygen species generation was also evaluated. Results: The khat extract showed an IC50 value of 86.5 μg/ml at 48 hours treatment. We have observed significant early apoptosis events by intervened acridine orange within the fragmented DNA with bright green fluorescence upon treatment. The Bcl-2 expression in the treatment with IC50 concentration of khat extract for 24, 48 and 72 hours of incubation significantly decreased with increase in bax level. The increased activation of caspase-3/7 was significantly observed upon treatment together with significant increase of ROS was detected at 24 and 48 hours treatment. Conclusion: Collectively, our results provide insight into the mechanisms by which Catha edulis leaves mediate cell death in cardiomyocytes.