Heavy metal contamination in food endangers human health. Probiotics can protect animals and human against heavy metals, but the detoxification mechanism has not been fully clarified. Here, mice were supplemented with Pediococcus acidilactici strain BT36 isolated from Tibetan plateau yogurt, with strong antioxidant activity but no chromate reduction ability for 20 days to ensure gut colonization. Strain BT36 decreased chromate accumulation, reduced oxidative stress, and attenuated histological damage in the liver of mice. 16S rRNA and metatranscriptome sequencing analysis of fecal microbiota showed that BT36 reversed Cr(VI)-induced changes in gut microbial composition and metabolic activity. Specifically, BT36 recovered the expressions of 788 genes, including 34 inherent Cr remediation-relevant genes. Functional analysis of 10 unannotated genes regulated by BT36 suggested the existence of a new Cr(VI)-reduction gene in the gut microbiota. Thus, BT36 can modulate the gut microbiota in response to Cr(VI) induced oxidative stress and protect against Cr toxicity.