Bacterial membrane vesicles (MVs) are used as a tool for intercellular communication and seem essential for bacterial survival. However, few data are available on MVs generated byStreptococcus mutans, which is the main aetiological agent of dental caries. The present study presents an integrated proteomics and metabolomics analysis of MVs isolated fromS. mutansat initial pH values of 7.5 and 5.5 and explores their function. The results showed thatS. mutansreleases more MVs with smaller diameters under acidic conditions than under neutral conditions. Proteomic analysis showed 344 common vesicular proteins, including various virulence factors. The expressions of 140 individual proteins and 37 metabolites were altered as a result of culturingS. mutansat different pH values. Co-analyses of proteomic and metabolomics data indicated that ABC transporters underwent significant changes under acid pressure. We concluded thatS. mutansproduced MVs at different pH values to carry proteins associated with cariogenesis. Moreover, the alterations ofS. mutansMVs under acid pressure were associated with ABC transporters. These results increase our knowledge ofS. mutansMVs and imply thatS. mutansMVs may play a functional role in carious infection.