Following dietary intake, food-derived compounds undergo metabolic conversion and absorption in the gastrointestinal tract, leading to systemic distribution and interaction with biological systems. These interactions can produce diverse physiological effects, maintaining homeostasis and, in some cases, offering health benefits. Among the various molecular targets, proteins are particularly important due to their central roles in intracellular signaling and enzymatic activity. The bioactivity of many food-derived compounds is thought to arise from their ability to interact with specific target proteins, either on the plasma membrane or within the cell(s). These interactions may be direct, via covalent or non-covalent binding, or indirect, through modulation of redox balance or signaling pathways. Accumulating evidence suggests that modulation of membrane-bound receptors is a key mechanism by which dietary compounds exert functional effects. By influencing receptor activity, these compounds can alter downstream signaling, contributing to physiological regulation and disease prevention. This chapter reviews insights into the molecular mechanisms through which food-derived compounds regulate membrane receptor function.