Background/Aim: Rhenium(I)-diselenoether (Re-diSe) is a drug under development for the treatment of metastatic cancers, with selective inhibitory effects on MDA-MB231 cancer cells compared to normal HEK-293 cells, and with greater effects than its diselenide (di-Se) ligand. Rhenium (Re) compounds inhibit cathepsins, which are important proteolytic enzymes in cancer. This study investigated the effects of Re-diSe and di-Se on the production of cathepsins B and S in MDA-MB231 malignant and HEK-293 normal cells and their inhibitory effects following treatment with different doses for 72 h. Materials and Methods: Elisa tests were used to assay the amount of cathepsins B and S in the medium of cultures. Results: Re-diSe, but not diSe affected the viability of malignant cells and the expression of cathepsins B and S. Conclusion: To the best of our knowledge, this is the first demonstration that Re-diSe may decrease the production of cathepsins B and S in cancer cells at doses as low as 10 μM. © 2022 Elsevier B.V., All rights reserved.