Background: While structured caloric restriction can improve metabolic health, excessive or prolonged dietary restriction (“over-dieting”) is increasingly prevalent due to aesthetic, social, and clinical pressures. Emerging evidence indicates that chronic energy deprivation may paradoxically exacerbate metabolic dysfunction and promote multisystem pathology Objective: This review critically evaluates the pathophysiological mechanisms, endocrine adaptations, pharmacological implications, and systemic consequences of excessive dietary restriction, integrating narrative synthesis with systematic trend-based evaluation (2020–2025).Methods: A structured literature search was conducted in PubMed, Scopus, and Web of Science (January 2020–January 2025). Keywords included “caloric restriction,” “over-dieting,” “metabolic adaptation,” “hypothalamic dysfunction,” “HPA axis,” “insulin resistance,” “gut microbiome,” and “nutritional deficiency.” Inclusion criteria comprised peer-reviewed human and translational studies. Data were synthesized thematically.Results: Excessive caloric restriction induces adaptive thermogenesis, neuroendocrine dysregulation (HPT, HPA, HPG axes), mitochondrial stress, micronutrient deficiencies, and gut microbiome alterations. These alterations contribute to metabolic inflexibility, sarcopenia, reproductive dysfunction, cardiovascular remodeling, neuropsychiatric disturbances, and immune suppression. Pharmacological agents such as GLP-1 receptor agonists and appetite suppressants may exacerbate nutrient deficits when combined with extreme restriction.Conclusion: Over-dieting represents a clinically under-recognized contributor to metabolic and systemic disease. Personalized, physiologically aligned dietary strategies and careful pharmacological monitoring are essential to prevent long-term harm