Punica granatum (Pomegranate fruit) and its constituents are proven effective against various cancer types. However, a kinome-wide screening for the active phytochemicals against kinases is not reported. This study aims in validating pomegranate fruit extract (PFE) against acute myeloid leukemia (AML) cells, and computationally identifying the phytochemicals interacting with active kinases. PFE was made with Soxhlet extractor using absolute ethanol. Gas-chromatography-mass spectroscopy (GC-MS) for phytochemical identification and MTT assay for cytotoxicity in AML (THP-1, TF-1 and HL-60) cells were performed. Apoptosis, CDK5 and CDK8 were assessed with flow cytometry. Kinase profiling was performed using In silico kinome screening. GC-MS analysis revealed 38 bioactive phytochemicals in PFE including pyrazoles, aldehydes, phenols, esters, pyranosides, and octadecadienoic acids. The extract inhibited the AML cell proliferations with GI