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Hydrogen peroxide (H₂O₂) has a major function in host-microbial interactions. Although most studies have focused on the endogenous H₂O₂ produced by immune cells to kill microbes, bacteria can also produce H₂O₂. How microbial H₂O₂ influences the dynamics of host-microbial interactions is unclear. Here we show that H₂O₂ released by Streptococcus pneumoniae inhibits inflammasomes, key components of the innate immune system, contributing to the pathogen colonization of the host. We also show that the oral commensal H₂O₂-producing bacteria Streptococcus oralis can block inflammasome activation. This study uncovers an unexpected role of H₂O₂ in immune suppression and demonstrates how, through this mechanism, bacteria might restrain the immune system to co-exist with the host.