Metabolomics is maturing as an experimental approach in nutrition science, and it is a useful analysis for revealing systems biology outcomes associated with changes in diet. A major goal of this review is to present the rapidly evolving body of scientific literature that seeks to reveal connections between an individual’s metabolic profile and experimentally manipulated or naturally varied dietary intakes. Metabolite profiles in tissue, serum, urine, or stool reflect changes in metabolic pathways that respond to dietary intervention which makes them accessible samples for revealing metabolic effects of diet. Three broadly defined areas of investigation related to dietary-metabolomic strategies include: (1) describing the metabolite variation within and between dietary exposures or interventions; (2) characterizing the metabolic response to dietary interventions with respect to time; and (3) assessing individual variation in baseline nutritional health and/or disease status. An overview of metabolites that were responsive to dietary interventions as reported from original research in human or animal studies is provided and illustrates the breadth of metabolites affected by dietary intervention. Advantages and drawbacks for assessing metabolic changes are discussed in relation to types of metabolite analysis platforms. A combination of targeted and non-targeted global profiling studies as a component of future dietary intervention trials will increase our understanding of nutrition in a systems context.