AbstractFractionated extracts of persimmon (Diospyros kaki) peels were studied for cytotoxic activity, multidrug resistance (MDR) reversal activity, anti‐human immunodeficiency virus (HIV) activity and anti‐Helicobacter pylori (H. pylori) activity. The potent cytotoxic activity against human oral squamous cell carcinoma cells (HSC‐2) and human submandibular gland tumor (HSG) cells was found in the acetone fractions (A4 and A5) with IC50 ranging from 21 to 59 µg/mL. However, the cytotoxic activity was not correlated with the radical intensity of the fractions. Three 70% MeOH extract fractions (70M2‐4) produced radical and efficiently scavenged the O2− produced by hypoxanthine and xanthine oxidase reaction. All of the fractions tested were not effective for anti‐H. pylori and anti‐HIV. Fractions H3 and H4 of hexane extract, and M2 and M3 of MeOH extract showed a remarkable MDR reversal activity comparable with that of (±)‐verapamil (a positive control). These results indicate the therapeutic value of persimmon peel extracts as potential antitumor and MDR‐reversing agents. Copyright © 2003 John Wiley & Sons, Ltd.