Mushrooms have a long history of use in traditional medicine, and hundreds of novel constituents in mushrooms with miraculous biological properties have been identified recently. Although diverse effects for medicinal use of mushrooms such as anticancer activity are proven, their reversal activities of drug resistance in cancer cells was rarely reported so far. In the search for novel medicinal use of mushrooms, we tested the multidrug resistance (MDR) reversal activities of diverse mushrooms collected from Korea. Among, the mushroom extracts tested, Cantharellus cibarius (M02) and Russula emetica (M12) revealed MDR reversal activities of paclitaxel in the P-glycoprotein (Pgp)-positive HCT15 and MES-SA/dX5 cancer cells, but not in the Pgp-negative A549 and MES-SA cancer cells. In addition, these mushrooms also enhanced the cytotoxicity of doxorubicin, another well-kwown Pgp-associated anticancer drug against MES-SA/DX5 cells, but not against MES-SA cells. Meanwhile, the cytotoxicity of cisplatin, a well-known Pgp-non-associated anticancer drug, was not affected by the mushrooms all the cells tested. From these results, we suspected that some ingredients of M02 and M12 have Pgp-associated MDR reversal activities.