Background: Pomegranate is also named Punica granatum native to Asia which contains a number of bioactive compounds such as phenolics, flavonoids ellagitannins and minerals. Previous studies have reported the anticarcinogenic effects of Pomegranate via inducing apoptosis and inhibition of cell proliferation in various cancer types. Purpose: In this study, we aimed to identify the cytotoxic and apoptotic effects of pomegranate extracts on U266 multiple myeloma cells. Methods: The cytotoxic effects of P. granatum leave, stem and flower on U266 cells were conducted via MTT cell proliferation assay. Then, apoptotic effects of P. granatum leave, stem and flower extracts on U266 cells were tested by loss of mitochondrial membrane potential and location of phosphotidylserine. Cell cycle analysis by flow cytometry was also performed to obtain cell populations in different phases by flow cytometry. Results: P. granatum extracts inhibited proliferation on U266 cells in a dose-dependent manner. We determined 87-, 88-, and 82% decreases in proliferation of U266 cells exposed to 500 μg/ml P. granatum leave, 500 μg/ml P.granatum stem and 100μg/ml P. granatum flower extracts for 72 hours, respectively, as compared to untreated cells. Annexin-V analysis revealed that there were 13-, 17-, and 19 fold increases in apoptotic cell population of U266 exposed to 500-, 750-, and 1000 μg/ml P. granatum leave extract, 16and 27 fold increases in apoptotic cell population exposed to 750-, and 1000 μg/ml P. granatum stem extract whereas 1.6and 3.5 fold increases in apoptotic cells exposed to 50 and 100 μg/ml P. granatum flower extract for 72 hours, respectively, as compared to control group cells. Loss of mitochondrial membrane potential analyses also confirmed apoptosis results. Summary/conclusion: These results documented cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells. Pomegranate induced apoptosis through deformation of mitochondrial membrane potential and increasing cell cycle arrests.