Membrane transporter proteins (the ABC transporters and SLC transporters) play pivotal roles in drug absorption and disposition, and thus determine their efficacy and safety. Accumulating evidence suggests that the expression and activity of these transporters may be modulated by various phytochemicals (PCs) found in diets rich in plants and herbs. PC absorption and disposition are also subject to the function of membrane transporter and drug metabolizing enzymes. PC–drug interactions may involve multiple major drug transporters (and metabolizing enzymes) in the body, leading to alterations in the pharmacokinetics of substrate drugs, and thus their efficacy and toxicity. This review summarizes the reported in vitro and in vivo interactions between common dietary PCs and the major drug transporters. The oral absorption, distribution into pharmacological sanctuaries and excretion of substrate drugs and PCs are considered, along with their possible interactions with the ABC and SLC transporters which influence these processes.