The inhibition or induction of hepatic cytochrome P450 3A4 (CYP3A4) enzyme associated with herbal medicines such as I'm-Yunity (Coriolus versicolor) can result in clinically significant herb-drug interactions. The active ingredient of I'm-Yunity is believed to be polysaccharopeptide polymer (PSP). Drug interactions between I'm-Yunity and other medications or supplements are yet to be investigated. The objective of this single-treatment, one-period, three-phase, open-labeled study was to evaluate the ability of I'm-Yunity to inhibit or induce CYP3A4 in 12 healthy adult volunteers (8 women and 4 men) aged between 23 and 54 years through the use of a CYP3A4-specific assay, the erythromycin breath test (EBT). EBT measurements are reported as percentage of 14C-Erythromycin metabolized/hr. Participants were given a 14-day supply of I'm-Yunity and instructed to take 1200 mg, three times daily with meals. Comparisons of all subjects' mean CYP3A4 activities were performed with the EBT before and after taking I'm- Yunity. Results revealed a mean EBT change (SD) from baseline of 0.08% (0.56%) 14C-Erythromycin metabolized/hr, which was not significant (p = 0.63). Therefore, 14 days of exposure to I'm-Yunity was not associated with clinically significant CYP3A4 inhibition or induction, suggesting that short-term administration of I'm-Yunity with medications primarily metabolized by CYP3A4 is safe and not expected to be associated with significant herb-drug interactions. However, it is still unknown whether interactions exist between I'm-Yunity and other medications metabolized by other CYP450 isozymes or enzyme/transporter systems.