Metabolomics techniques offer the possibility to semi-quantitatively examine a wide scale of endogenous metabolites potentially affected by the consumption of whole grain. Various metabolite analysis applications, including both mass spectrometry and NMR-based technology, have been utilized in this research field. This chapter focuses on the published metabolomics research regarding endogenous metabolic changes observed in studies involving whole grain consumption and impact on health. The evidence from prospective, observational studies on the impact of whole grains on human health is convincing as high consumption has been associated with reduced risk of major chronic diseases including cardiovascular diseases. Very few metabolomics approaches have been undertaken on epidemiological studies involving examination of dietary intake of whole grain products. While plasma and urine are the predominant sample materials available from human studies, animal trials are often necessitated in order to find out more detailed information on the perturbations caused by the dietary differences on cellular metabolism.