Trace elements, though required in minute quantities, play fundamental roles in maintaining physiological homeostasis, enzymatic functions, and cellular integrity. Essential trace elements, such as zinc, copper, selenium, iron, and manganese, act as cofactors for key enzymatic reactions, regulate redox balance, and contribute to immune function, neuroprotection, and metabolic processes. Dysregulation of these elements, either through deficiency or excess, has been implicated in a wide spectrum of diseases, including cardiovascular disorders, neurodegenerative conditions, diabetes, cancer, and others. Zinc and copper homeostasis are critical for immune competence and oxidative stress modulation, while selenium exerts profound effects on redox signalling and thyroid function. Iron imbalance is closely associated with anemia, oxidative stress, and neurodegeneration, whereas manganese plays a pivotal role in mitochondrial function and antioxidant defense. Emerging research highlights the role of trace element interactions, metal ion transporters, and metalloproteins in disease pathophysiology. This chapter explores the intricate biochemical and molecular mechanisms through which trace elements can influence health and diseases, emphasizing their diagnostic and therapeutic potential in precision medicine and clinical nutrition. Understanding the homeostatic regulation and pathophysiological implications of trace elements may provide novel insights into disease prevention and targeted interventions.