The “Drug–Non-drug Interactions Concept,” including drug-disease or drug-food interactions which has been widely studied over the past decades in which the patient has been the central focus of studies, is becoming an increasingly current subject. In this context, it is known that some diseases can affect organs associated with drug metabolism, reducing the success rate of treatments. A similar effect is observed during patient aging, where age should be considered as an additional factor in the patient’s pathology. In other situations, components of patients’ diets can interfere with drug pharmacokinetics, affecting their pharmacodynamic profile and resulting in treatment failures. In this chapter, an overview is provided focusing on this issue, explaining the interactions and the drug classes most affected due to patient diet components, including antivirals, anti-inflammatories, antidiabetics, and anticancers among others. Additionally, how these interferences affect CYP-related enzymes, organic anion transporters (OATs), intestinal P-glycoprotein, and human serum albumin (HSA) are discussed. Phenolic and flavonoid compounds are widely studied, as they are phytochemicals easily found in various food preparations. Furthermore, their interactions with physiological macromolecules are presented, making clear the chemical nature of these interactions. Finally, a perspective on the theme is presented at the end of this chapter, as well as some questions are provided to aid in understanding this relevant topic.