In an era of “omic” sciences and big data analysis, many research areas still constitute new ground for the application of such nontraditional strategies, which may potentially provide significant and rapid advances in scientific knowledge. Biomaterial research is an example of this, in particular regarding the potential of metabolomics in providing further insight into various steps of biomaterial development, from its preparation to the assessment and fine-tuning of its performance in a biological context. This review firstly presents the basic concepts of metabolomics and the analytic strategies entailed, while briefly stating the major advances it has fostered in health research. The recent translation of metabolomics to biomaterial research is here illustrated in three major aspects: (1) stem cell (SC) research, based on the link between metabolic traits and SC function or differentiation, amenable to biomaterial guidance; (2) measurement and monitoring of biomaterials’ biological performance; and (3) follow-up and optimization of the synthesis of biopolymers used as biomaterials. Furthermore, the present text attempts to provide the reader with a view of possible future developments in the use of metabolomics to enhance biomaterial research, from improving biomaterial formulations to fostering new strategies for the clinical follow-up of biomaterial interventions.