Multiple myeloma (MM) cancers are 10% of hematological cancers. Leukemia ARH-77 is a malignancy like MM with a worse course of disease and the survival rate from it is very low. Therefore, ARH-77 is a commonly used model for antitumor agent studies. Polyphenolic compounds, such as resveratrol, rutin and rosmarinic acid, have many protective roles, but there is no comparative study about these three polyphenolic compounds on ARH-77. In the present study, we investigated the cytotoxic effects of resveratrol, rutin and rosmarinic acid on ARH-77. Toxic concentration ranges were determined by the brine shrimp lethality test on Artemia salina. In addition, for determination of their cytotoxic effects, MTT and NR methods were used for ARH-77. Resveratrol caused significant reduction in both mitochondrial and lysosomal activities compared with the control group. Maximum inhibition values were detected on mitochondrial and lysosomal activity with 200 pM concentrations after 48 hours. After a 24 hours incubation period, rutin showed cytotoxic effects, particularly with 50, 100 and 200 lM concentrations. Rosmarinic acid also decreased the mitochondrial activity with the same concentrations. Resveratrol showed higher cytotoxic effects than rutin and rosmarinic acid. According to our study, polyphenolic compounds such as rutin, resveratrol and rosmarinic acid may hold promise in multiple myeloma treatment with further investigations.