The last decade made considerable efforts in unravelling mechanisms underlying anticancer, antitoxic and anti cell death potential of bioflavonoids, but their in vivo biodistribution, biolocalization and biotransformation remains unclear. Our lab has been a trendsetter in this direction and this study was designed to investigate the bioavailability and localization of some well researched bioflavonoids in various target organs in vivo. Among thousands of flavonoids, Curcumin (Cur), Silymarin (Sil) and Grape seed Proanthocyanidin extract (GSPE) were chosen because of their powerful anti-toxic properties and because of their success to become candidates for clinical trials. In order to determine the concentrations of these bioflavonoids in multiple vital target organs, 3 months old female ICR mice (26–42 g) were gavaged with 100 mg/kg solutions of Curcumin (Cur), Silymarin (Sil) and Grape seed Proanthocyanidin extract (GSPE) and sacrificed 24 hours later. Blood was collected upon sacrifice to analyze the serum chemistry and concentrations of these bioflavonoids. The total phenolic content in the serum and several vital target organs (liver, heart, kidney and duodenum) were determined based on modified Folin Ciocalteu method (Singleton and Rossi 1965). Analysis of the vital target organs showed that the bioavailability of these flavonoids were in the following order: SIL > GSPE > CUR. Besides analyzing the target organs, serum concentrations of these flavonoids were also determined at 0, 2, 4 and 24 hrs. Analysis of serum enzymes (ALT, BUN AND CK) showed near normal levels with slight increase in CK activity. These studies provide a comprehensive picture of the bioavailability profile of these bioflavonoids, and may have been the first such systematic in vivo study to determine the bioavailability profile of these natural products. All these are well established and acclaimed antioxidants with demonstrated antitoxic and anticancer properties in humans as well as in a variety of experimental animals. However, the final outcome of well-controlled clinical trials can only justify the usefulness of these compounds in clinical settings.