Updated project metadata. This project investigates the changes in proteome profiles that occurred in the same set of S. mutans wild-type and lrgAB mutant samples used in our recently published RNA-seq study. To this end, mass spectrometry-based label-free quantitative proteomics, a technology known to enable comprehensive identification and quantification of complete bacterial proteomes, was adapted to study changes in S. mutans intracellular protein levels in response to aeration, heat, and vancomycin stress. Furthermore, the degree of correlation between S. mutans protein abundance profiles and gene expression changes was determined. Further understanding of these combined “-omics” data at the cellular or molecular level will enhance our knowledge of Cid/Lrg-mediated cellular responses of S. mutans to adverse environments. Furthermore, these “-omics” data will serve as a valuable resource that can be mined to help clarify the role of the S. mutans stress response and physiological activity to its dynamic survival in the oral cavity.