Active hexose correlated compound (AHCC), a Basidiomycotina extract, is a well-tolerated nutritional supplement with no reported adverse effects. It has demonstrated potential antitumor activity and immune modulator activity. However, there is no current information regarding its metabolism and the potential for drug-drug interactions for AHCC in combination with chemotherapy. The objective of this study was to characterize AHCC hepatic metabolism, specifically involving the potential for drug interactions with selected chemotherapy agents. High-throughput cytochrome P-450 (CYP450) metabolism inhibition experiments were conducted in vitro evaluating CYP450 3A4, 2C8, 2C9, and 2D6 followed by an evaluation of AHCC as a substrate of these same isoenzymes. An ex vivo model of cryopreserved human hepatocytes was used to evaluate the CYP450 metabolism induction potential of AHCC for CYP450 3A4, 2C8/2C9, and 2D6. No inhibition of CYP450 activity was observed in presence of AHCC; however, AHCC was a substrate of CYP450 2D6. The CYP450 induction metabolism assays indicate that AHCC is an inducer of CYP450 2D6. AHCC does have the potential for drug-drug interactions involving CYP450 2D6, such as doxorubicin or ondansetron; however, the overall data suggest that AHCC would be safe to administer with most other chemotherapy agents that are not metabolized via the CYP450 2D6 pathway.