The food matrix is a complex system encompassing all constituent elements in food production. It influences the digestibility of these elements through direct interactions and affects the digestive environment. Furthermore, the gastrointestinal system possesses precise mechanisms that efficiently process dietary components into essential nutrients, effectively preventing the onset of abnormal immune responses or dysfunctional host reactions in most instances. However, the incidence of adverse food reactions is constantly increasing, and evidence indicates that this process is environmental. Adverse reactions can be categorized as toxic or nontoxic. Toxic reactions are dose-dependent and can result from natural compounds, processing-induced substances, or contaminants. Nontoxic reactions like food intolerance and hypersensitivity depend on individual susceptibility and evoke specific pathological and physiological responses. This review aims to elucidate the mechanisms underlying the occurrence of immune- (food allergies and sensitivities) and non-immune-mediated (food intolerance) reactions, emphasizing the fundamental distinctions between these two categories. Enhanced comprehension and distinction of these mechanisms will significantly contribute to advancing preventive and therapeutic approaches and establishing guidelines for food labeling concerning immune-mediated reactions.