Down syndrome is the most common autosomal aberration among liveborns, characterised by several clinical features and metabolic disturbances. Aminoacid pathways abnormalities and defective oxidative balance are the most common metabolic problems in Down Syndrome. To evaluate the biochemical responses of children with Down Syndrome to a nutritional regimen supplemented with aminoacids, vitamins and polyunsaturated fatty acids, we submitted 86 subjects divided in two groups (0-6 and 6-12 years) to the dosage of plasma levels of aminoacids, antioxidant enzymes activities and reactive oxygen species, before and after 12 months of such nutritional supplementation and in relation to normal controls. The results obtained showed a tendency towards the values of normal subjects with statistically significant differences. Although other studies must be performed to confirm and define such report, our experience supports the usefulness of a nutritional supplementation with aminoacids, vitamins and polyunsaturated fatty acids, also considering the absence of side effects.