Due to their rising popularity, herbal supplements have created a specific niche for themselves between the food and the drug industry. Due to their categorization as dietary supplements, they lack scientific seriousness where as on the other hand they act like unregulated drugs with potential effects. Finding scientific data of questionable accuracy for herbal supplements is not uncommon, which is usually designed to sell products rather then provide unbiased information. Hence, development of performance standards based on the bioavailability of the active components of herbal extracts promises to be an attractive solution towards regulating the inflow of meaningful products in the herbal supplement market. Solubility, partition coefficient and permeability are the fundamental properties for studying drug absorption. Top selling herbal extracts from the United States that included Kava, Ginkgo biloba, Milk thistle, Ginseng, Black cohosh, Garlic, Valerian, and Echinacea were selected and in silico descriptors such as CLogP, minimal cross-sectional area, polar surface area and in vitro permeability using the Caco-2 cell model and SimBioDAS® of their active components, determined. Based on the interparameter relationships between the minimal cross sectional area, CLogP, polar surface area and the in vitro permeability of the active components, bioavailability/bioequivalence markers were predicted for Kava, Ginkgo biloba and Milk thistle. Kawain was predicted as a marker for Kava, Ginkgolide B for the ginkgo terpenes and quercetin for the flavonol glycosides in Ginkgo biloba and silycristin as a marker for Milk thistle (silymarin). Silymarin comprising of isomers silycristin, silydianin, silybin A, silybin B, isosilybin A and isosilybin B was selected as a representative extract for further confirmation of marker prediction. Equilibrium solubility, experimental octanol-water partition coefficient values, and assay and in vitro dissolution profiles were determined for each of the active isomers in extract and market products respectively. The pharmacokinetics and absolute bioavailability of each of the active isomers was determined in male Sprague Dawley rats following intravenous and oral administration of the silymarin extract. Equilibrium solubility values indicated that all the silymarin isomers were practically insoluble, and silycristin and silydianin had relatively higher solubility values as compared to the other isomers. Experimental partition coefficient values correlated with the predicted partition coefficient (CLogP) with an r² of 0.834. Based on their equilibrium solubility and the partition coefficient (experimental and predicted) the active isomers were classified according to the Biopharmaceutic Classification System (BCS). Thus, isomers silybin A, silybin B, isosilybin A and isosilybin B were classified as Class II compounds (High PermeabilityLow Solubility) where as silydianin was classified as a Class IV compound (Low Permeability-Low Solubility). Silycristin was classified as a intermediate between Class II and Class IV. Absolute bioavailability (F) for silycristin was found to be the lowest (0.15±0.1), followed by silybin A (0.20±0.04) followed by silybin B (0.62±0.08). Silycristin being one of the least permeable and bioavailable component, was selected as a marker for silymarin, further confirming its prediction based on the correlations between the in silico descriptors and in vitro permeability. Pharmacokinetic parameters such as area under the curve, half life, volume of distribution, clearance and F for the components suggest significant differences between not only the silymarin isomers but also diastereomers of silybin (A and B) and isosilybin (A and B). Selection of bioavailability-bioequivalence markers, based on their least permeability/bioavailability, proves to be the most conservative and meaningful approach towards standardization of complex mixtures such as herbal extracts and supplements.