P-glycoprotein(P-gp) is an ATP-dependent multidrug efflux pump that acts as a major obstacle for oral drug delivery and cancer therapy.  Recent reports have provided evidence that excipients often used in pharmaceutical formulations, such as Pluronic and TPGS, also have inhibitory effects on P-glycoprotein.  Because inhibition of ef?ux transporters by polymeric inhibitors may dramatically increase the bioavailability of P-gp substrates with negligible side effects, identification of the mechanism and their structure activity relationship  is therefore of significant importance for pharmaceutical development.  Other than competitive inhibition for traditional inhibitors, polymeric inhibitors may modify P-gp function through alterations on membrane fluidity, inhibition of P-gp ATPase, depletion of intracellular ATP and down-regulating of P-gp expression.  In the   present review, the inhibition mechanism of potential polymeric inhibitors and their structure activity relationship will be discussed along with a brief introduction to the established methodologies.