**Abstract**

P-glycoprotein (P-gp) is an active member of the ATP Binding Cassette (ABC) protein subfamily which effluxes a wide range of therapeutic drugs out of the cells commonly known as multidrug resistance. But its protective action towards the normal cells and efflux of the toxic and foreign substances is remarkable. Hence the efflux of the P-gp is a crucial step to overcome for the success of the therapy and in the drug discovery process. Modification of the action of the P-gp through various inducers, inhibitors or the genetic polymorphism is the commonly used methods. When it comes to the inhibitor part the natural inhibitors use is more safe and economical as compared to the synthetic ones. Here we review at the mechanism of action and the pharmacokinetic profile of P-gp, how the P-gp engaged in the Multidrug resistance, the strategy to overcome from its action by using natural inhibitors and formulation perspectives.

**Keywords:** P-glycoprotein, multidrug resistance, mechanism of action, pharmacokinetics, P-gp inhibitors, natural inhibitors
