Metabolic dysfunctions have not been extensively studied in ASD despite the fact that chronic biochemical imbalance is often a primary factor in the development of several neurological diseases. Substantial percentages of autistic patients display peripheral markers of mitochondrial energy metabolism dysfunction, such as elevated lactate and alanine levels in blood and serum carnitine deficiency. We assess the reported biochemical changes in the blood and evidence based on the exploration of brain imaging studies. Even though alterations in mitochondrial and cellular energy metabolism are not specific for ASD, they indicate the potential ethiopathological events. Evidence from several laboratories similarly indicates that biomarkers of oxidative stress may be increased in some autistic children. One of the best documented biochemical changes in ASD is a decrease in cellular glutathione (GSH) levels, a major intracellular antioxidant, and an increase in oxidized glutathione (GSSG). Alterations in methionine -homocysteine cycle have been studied in details in ASD. Significant changes in transmethylation and transsulfuration metabolites in plasma from autistic children were reported. The new finding indicates a significant decrease in methylation capacity and redox potential. Metabolic and mitochondrial defects may have toxic effects on brain cells, causing neuronal loss and altered modulation of neurotransmission systems. The observations of biochemical changes thus further support that the antioxidant therapy and supplementation with some vitamins could prevent and restore the energy metabolism of individuals with ASD. This chapter brings evidence of the impact of observed biochemical changes in ASD for potential amelioration of ASD symptoms and for evidence-based therapy.