Rooibos tea ( Aspalathus linearis) is a well-known South African herbal tea enjoyed worldwide. Limited reports indicate the potential of rooibos tea to alter the activity of certain cytochrome P450 (CYP450) isozymes. In this study, the phytochemical investigation of MeOH extract of A. linearis (leaves and stems) resulted in the isolation and characterization of 11 phenolic compounds. The MeOH extract exhibited significant inhibition of the major human CYP450 isozymes (CYP3A4, CYP1A2, CYP2D6, CYP2C9, and CYP2C19). The strongest inhibition was observed by the extract for CYP3A4 (IC