Some membrane transporters play essential roles in drug disposition. Hence, elucidation of factors that could affect activities of the transporters, such as genetic mutations or drugs, is quite important issues. Because they can accept diverse compounds as substrate, metabolomic analysis have been conducted to identify their endogenous substrates in the pharmacogenomic or drug-drug interaction (DDI) studies. Together with in vitro demonstration that they are substrates of drug transporters, the fact that pharmacokinetic parameters of a set of endogenous substrates of the drug transporters, such as area under the plasma concentration-time curve (AUC), or renal clearance (CL_R), are significantly associated with altered activities of the drug transporters supported that such endogenous substrates serve as clinical biomarker for the transporters. They are now highly expected to advance the DDI risk assessment of new chemical entities in clinical development. This presentation introduces the progress of the clinical biomarker studies of drug transporters (OATP1B, OCT2, and MATE1/2-K), and application to the DDI studies in healthy subjects and patients.