Active hexose correlated compound (AHCC) is an extract of a basidiomycete mushroom that is used as a supplement by some cancer patients undergoing chemotherapy; it is thought to enhance the therapeutic effects and reduce the side effects of select anticarcinogenic agents. AHCC has been reported to strengthen the anticancer effects of cisplatin (CDDP) and ameliorate its side effects in female BALB/cA mice inoculated with Colon-26 tumor cells. In this study, the role of AHCC in alleviating the side effects induced by several other anticancer drugs was explored in non-tumor-bearing mice receiving monotherapy with paclitaxel (TAX), or multi-drug chemotherapy with TAX plus CDDP, 5-fluorouracil (5FU) plus irinotecan, CDDP plus 5FU, or doxorubicin plus cyclophosphamide. Outcomes from the drug treatment groups with and without AHCC supplementation were compared to controls that received vehicle alone. The multi-drug treatments significantly reduced bone marrow cell viability in all groups and leukocyte count in all groups except for TAX+CDDP; these myelosuppresive effects were generally alleviated by AHCC. Hepatotoxicity and nephrotoxicity caused by the treatments that included TAX and CDDP were also significantly improved by AHCC. The death rate was 20 to 30 percent in all treatment groups except TAX+CDDP, and supplementation with AHCC greatly reduced or eliminated mortality. These results support the concept that AHCC can be beneficial for cancer patients receiving chemotherapy.