Several genistein derivatives comprising an isoflavonoid skeleton substituted with an alkyl chain and a sugar moiety show ability to inhibit proliferation of cancer cells in vitro at the concentration several-fold lower than genistein. In our previous studies we shown that these compounds influenced the mitotic spindle, blocked the cell cycle and induced apoptosis. The purpose of this study was to determine the relationship between structural modifications of genistein molecule and the intestinal disposition of its derivatives. Transport and metabolism of these compounds were studied in the human intestinal Caco-2 model. The results of our study indicate that transport and metabolism of genistein derivatives depend both, on the structure of the carbonyl linker and position of genistein molecule substitution. All new compounds showed higher permeability coefficient in comparison to genistein. Moreover, genistein derivatives described in this work were transformed in Caco-2 cells into glucuronide and sulfate metabolites.