The calcineurin inhibitor tacrolimus (TAC) shows inter-and intra-individual variability in blood levels and has a narrow therapeutic index. To reduce the chance of fluctuations in immunosuppressive activity and potential drug interactions, it is critical to keep track of drug concentrations. Cytochrome-P450 (CYP) isoenzymes CYP3A4 and CYP3A5, as well P-glycoprotein (P-gp) are involved in TAC bioavailability. TAC's interactions with herbal extracts are reviewed here, because with more people using TAC, it is becoming crucial to know which extracts, which are often part of self-medication, can alter TAC blood concentrations. TAC bioavailability was decreased when co-administered with St John's wort (SJW), cranberry, rooibos tea, and boldo in human models by induction of the CYP450 system and/or P-gp efflux pump, meanwhile, the TAC bioavailability was increased when co-administered with grapefruit juice (GFJ), schisandra, berberine, turmeric, pomegranate juice, pomelo, and ginger in human and or animal models by inhibition effect on CYP450 system and/or P-gp efflux pump. Thus, physicians and pharmacists should thoroughly educate their patients regarding the use of supplemental herbs before administering TAC. Furthermore, patients who are already undergoing TAC treatment should be informed about the possibility of dangerous interactions between herbal remedies and TAC.