The kidney and renal physiology is vital for the defence mechanism against potentially harmful food adulterants, contaminants xenobiotics and metabolic by-products that are eliminated by liver and via renal elimination pathways. Specifically, the secretory transporters located in the proximal tubule serve as primary factors influencing the disposition of xenobiotics including food contaminants, which encompass numerous nutraceuticals and foods. Over the last decade, significant advancements have been achieved by nephrology researchers in unravelling the role of renal transporters in the pharmacokinetics of various clinicals from food and pharmaceuticals. Moreover, several renal transporters have been identified as crucial sites for several clinically relevant drug-drug interactions. This book chapter commences with an exposition on renal drug management and provides pertinent equations necessary for calculating renal clearance, which includes both filtration and secretory clearance in detoxification. Furthermore, data concerning the localization, expression profiles, substrates, and inhibitors of renal drug transporters are systematically organized in tabular form. The recent draft guidance from the US Food and Drug Administration (USFDA) regarding drug-drug interactions, specifically in relation to the investigation of renal drug transporters, is discussed threadbare through this chapter for a lucid understanding of inherent processes and mechanisms involved and their subtle crosstalks physiologically for achieving homeostasis in the body.