Increased caloric intake associated with decreased physical activity and the presence of thrifty genes that are theoretically adapted to enhance the energy storage efficiency, cause metabolic changes that result in diet-related diseases or disorders. Such phenotypes are prevalent in populations of developed countries and their incidence is continuing to rise. Therefore, early diagnosis of diet-related diseases is an exciting field of research. The application of ‘omics’ technology, particularly metabolomics, has revealed the metabolic changes associated to diet-related diseases and also consequences of diet intervention in a global un-targeted way. The on-going development of dietary ideal models could elucidate the sequence of events, starting with the interaction between dietary habits and genetic adaptations that cause the metabolic changes induced as well as auxiliary symptoms and associated diseases. In this review, a range of mass spectrometry techniques applied to metabolomics of diet related diseases is discussed, including the combination of metabolomics with other studies to reveal systems properties of the diseases. Since it is difficult to set up a clinical study based on the probability of finding exploratory biomarkers to be applied in wide-population screening, many metabolomics studies have revealed biomarkers of 31 the complications of the disease, which could have power as prognostic biomarkers.