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Introduction Despite the significant developments occurring in the treatment of cancer, multiple myeloma remains the second haematological deadly disease. The aim of this study was to investigate the antiproliferative and apoptotic activities of Olea europaea L. cv Chetoui leaf and stem extracts (OLE and OSE) on human myeloma cells, given that plant compounds provide antitumor drugs. Methods Anti-cancer activity was tested on U266 human multiple myeloma cell line using MTT and trypan blue assays. Cell cycle analysis, cell death mechanism, mitochondrial membrane potential levels and caspases activities were assessed in U266 cells using flow cytometry. The nuclear morphology of U266 cells was observed using Hoechst 33342 using fluorescent microscopy. Results Our data revealed that treatment with OLE and OSE induced anti-proliferative effects on U266 myeloma cells in dose and time dependent manner. The IC50 of OLE and OSE were 55 and 35 μg/mL, respectively after 48 h of exposure. Interestingly, cell cycle analysis showed significant decrease of U266 cells in G1 phase related to significant increase in sub-G1 population after 24 h of extract treatment. Moreover, OLE and OSE significantly induced apoptosis in U266 cell line after 24 h of treatment by inducing mitochondria dysfunctions and caspase 3/7 expression. Conclusion To our knowledge this is the first paper to be conducted on olive stem extract. Our study showed that OLE and OSE had potent anti-multiple myeloma properties. This work may form the basis for further investigation on olive extracts as potential therapeutic agent on multiple myeloma.