<p><i>Bacillus cereus</i> is a significant foodborne pathogen whose infection can trigger gastrointestinal symptoms or systemic diseases in hosts, with severe cases potentially leading to sepsis or even death. In recent years, the misuse of antibiotics has led to varying degrees of drug resistance in foodborne pathogens, making the development of novel antimicrobial agents an urgent necessity. Natural active substances have become a focal point of current research due to their broad-spectrum and highly efficient antibacterial capabilities against foodborne pathogens. Prodigiosin (PG), initially garnering widespread attention in the pharmaceutical field for its multifunctional bioactivities, also demonstrates significant potential in the food industry. However, there is currently no reported research on the antibacterial effects of PG against <i>B. cereus</i>, its anti-infection mechanisms, and its impact on the host's intestinal microbiota. Based on this, our study focuses on PG as the research subject and <i>B. cereus</i> as the test strain, systematically investigating its therapeutic effect in <i>B. cereus</i>-infected mice. Additionally, we employed 16S rRNA-based microbiota analysis and metabolomics approaches to explore the effects of PG on the composition of the gut microbiota and metabolomic profiles. Collectively, PG exerts its therapeutic effects in <i>B. cereus</i>-infected mice by alleviating tissue damage, reducing inflammation, and modulating the abundance and diversity of the intestinal microbiota. These results highlight a novel strategy for alleviating <i>B. cereus</i> infections<i>.</i></p>