This chapter explores the complex interplay between diet and psychotropic medications, emphasizing how dietary elements can influence the efficacy, safety, and overall outcomes of psychopharmacotherapy. By examining mechanisms at the genetic, pharmacokinetic, and pharmacodynamic levels, the chapter highlights both positive and negative aspects of diet-drug interactions. Positive dietary interactions, such as the supportive role of omega-3 fatty acids, B vitamins, and magnesium, can enhance drug absorption, stabilize neurotransmitter function, and reduce inflammation, thereby complementing therapeutic outcomes. In contrast, certain foods and supplements, such as high-fiber meals, grapefruit juice, and St. John’s Wort, can interfere with drug metabolism, potentially causing adverse effects or diminishing drug efficacy. The chapter also addresses cultural and religious considerations, which shape dietary habits and influence dietary recommendations in diverse patient populations. Practical implications are provided to guide clinicians in integrating dietary assessment, tailored counseling, and multidisciplinary collaboration into routine mental health care, ensuring that dietary factors support rather than hinder psychopharmacotherapy. This integrative approach ultimately aims to foster personalized, effective, and holistic mental health treatment.