It is increasingly evident that the gut microbiota is involved in the regulation of multiple mammalian metabolic pathways through a series of interactive host-microbiota metabolic, signaling, and immune-inflammatory axes that physiologically connect the gut, liver, brain, and other organs. Correlation of the metabotypes with the gut microbial profiles derived from culture-independent molecular techniques is increasingly useful for deciphering inherent and intimate host-microbe relationships. Real-time analysis of the small molecule metabolites derived from gut microbial-host co-metabolism is essential for understanding the metabolic functions of the gut microbiome and has tremendous implications for personalized healthcare strategies. Metabolomics, an array of analytical techniques that includes high resolution NMR spectroscopy and chromatography-MS in conjunction with chemometrics and bioinformatics tools, enables characterization of the metabolic footprints of mammalian hosts that correlate with the microbial community in the intestinal tract. The metabolomics approach provides important information of a complete spectrum of metabolites produced from the gut microbial-mammalian co-metabolism and is improving our understanding of the molecular mechanisms underlying multilevel host-microbe interactions. In this review, the interactions of gut microbiota with their host are discussed and some examples of NMR- or MS-based metabolomics applications for characterizing the metabolic footprints of gut microbial-host co-metabolism are described. Advances in the metabolomic analysis of bile acids, short-chain fatty acids, and choline metabolism are also summarized.