Synthetic biology, an interdisciplinary field combining principles of biology and engineering, offers promising new therapeutic strategies for inherited metabolic disorders. Hereditary Fructose Intolerance (HFI) is one such genetic condition, classified as a rare autosomal recessive disorder. It arises from pathogenic variants in the ALDOB gene, which is responsible for producing aldolase B, an enzyme critical for breaking down dietary fructose. In individuals with HFI, the absence or malfunction of aldolase B leads to a harmful buildup of fructose-1-phosphate (F-1-P) within liver and kidney cells. This accumulation disrupts essential metabolic pathways, notably gluconeogenesis and glycogenolysis, ultimately triggering serious complications including hypoglycemia, hepatic injury, renal impairment, and lactic acidosis. Synthetic biology-based strategies are being explored to restore or compensate for the defective enzymatic function and mitigate the clinical impact of the disorder. HFI typically manifests in infancy following the introduction of fructose-containing foods, and if left untreated, can lead to irreversible organ damage. Current treatment strategies are limited to strict lifelong avoidance of fructose, sucrose, and sorbitol. This chapter explores the molecular etiology, clinical manifestations, diagnostic methods, and pathophysiology of HFI, with a strong focus on emerging synthetic biology-based interventions. These include gene therapy aimed at correcting ALDOB mutations, engineered gut microbiota capable of degrading fructose prior to absorption, and enzyme replacement therapy (ERT) using synthetic or recombinant aldolase B. Each of these approaches is evaluated in terms of feasibility, benefits, challenges, and ethical considerations. By addressing the underlying enzymatic and genetic defects, synthetic biology holds the potential to shift HFI treatment from dietary management to root-cause intervention. Continued advancements in genetic engineering, microbial design, and biotherapeutic delivery systems may enable the development of curative or substantially disease-modifying therapies for HFI and related metabolic disorders in the near future.