Recent research indicates that the human microbiota play key roles in maintaining health by providing essential nutrients, providing immune education, and preventing pathogen expansion. Processes underlying the transition from a healthy human microbiome to a disease-associated microbiome are poorly understood, partially because of the potential influences from a wide diversity of bacterium-derived compounds that are illy defined. Here, we present the analysis of peptidic small molecules (SMs) secreted from bacteria and viewed from a temporal perspective. Through comparative analysis of mass spectral profiles from a collection of cultured oral isolates and an established in vitro multispecies oral community, we found that the production of SMs both delineates a temporal expression pattern and allows discrimination between bacterial isolates at the species level. Importantly, the majority of the identified molecules were of unknown identity, and only ∼2.2% could be annotated and classified. The catalogue of bacterially produced SMs we obtained in this study reveals an undiscovered molecular world for which compound isolation and ecosystem testing will facilitate a better understanding of their roles in human health and disease.