In a three-period RCT 16 healthy participants were randomised to Silybum marianum or control. All participants received initial dosing of indinavir and baseline indinavir levels were obtained (area under the curve, AUC_0–8) (phase I). The active group was then given 450 mg S. marianum extract capsules to be taken t.i.d. from day 2 to day 30. The control group received no plant extract. On day 29 and day 30 indinavir dosing and sampling were repeated in both groups as before (phase II). After a washout period of 7 days, indinavir dosing and sampling were repeated as before (phase III). There were no significant between-group differences. Active group mean AUC_0–8 indinavir decreased by 4.4% from phase I to phase II in the active group, and by 17.3% in phase III. Control group mean AUC_0–8 decreased by 21.5% from phase I to phase II and by 38.5% of baseline at phase III. A meta-analysis of three S. marianum/indinavir trials revealed a non-significant pooled mean difference of 1% in AUC_0–8.