A series of novel diaryl ether analogs possessing gallate moiety were synthesized and NF-κB inhibitory activity and cytotoxicity were evaluated. NF-κB luciferase activities in prostate LNCaP and colon cancer HCT116 cells showed that 2a, 2c, 2d, 2g, and 2i had potent to moderate inhibitory activities. In addition, 2a exerted more potent cytotoxicity than the reference compound, obovatol, against prostate (LNCaP and PC-3) and colon cancer (HCT116 and SW620) cells.