Dietary isoflavones, popularly known as phytoestrogens, represent one of the most biologically active classes of flavonoids.
Numerous in vitro and in vivo studies provide convincing evidence regarding their beneficial effects on human health. These isoflavones
are increasingly being investigated as potential alternate therapies for a range of hormone-dependent conditions, including cancer, menopausal
symptoms, osteoporosis and cardiovascular diseases. However, they exhibit poor oral bioavailability which limits their clinical
utility in humans. The reason being, they are substrates of a plethora of enzymes and transporters and undergo extensive conjugative metabolism
which facilitates their rapid elimination from biological systems. In addition, a number of experimental studies have also revealed
that these isoflavones are potent inhibitors of various cytochrome P450 isoforms and transporters which play an important role in
the disposition of many commonly prescribed drugs. Thus, there arise chances of observing clinically relevant herb-drug interactions
which could sometimes be life-threatening. This review gives a comprehensive understanding of these dietary phytoestrogens with regard
to their absorption, biodistribution and the role of enzyme-transporter interplay affecting their disposition in biological systems. Further,
the effects of these phytoestrogens on the activity and kinetics of drug metabolizing enzymes and various clinically relevant influx/efflux
transporters and the resulting diet-drug interactions have also been discussed.