Schistosoma japonicumcauses serious pathological organ damage and alteration of the intestinal microbiome in the mammalian host, threatening the health of millions of people in China.Bacillus amyloliquefacienshas been reported to be able to alleviate the damage to the gut and liver and maintain the homeostasis of the intestinal microenvironment. However, it was unclear whetherB. amyloliquefacienscould alleviate the hepatic and intestinal symptoms caused byS. japonicum. In this study, the intragastric administration ofB. amyloliquefacienswas performed to treatS. japonicum-infected mice during the acute phase. Histopathological analysis and 16S rRNA gene sequencing were used to evaluate the pathological damage and changes in the intestinal microbiome. The results of the study showed thatB. amyloliquefacienstreatment significantly reduced the degree of granuloma and fibrosis in infected mice. Additionally, recovery of diversity in the intestinal microbiome, decrease in the relative abundance of potential pathogenic bacteria such as Escherichia–Shigella, and reshaping of the interactive network between genera in the intestine were also observed after treatment withB.amyloliquefaciens. Our findings indicated that treatment withB. amyloliquefacienseffectively alleviated the pathological injuries of the liver and intestine in mice infected withS. japonicumby modulating the intestinal microbiome, implying that this probiotic can function as an effective therapeutic agent against schistosomiasis. We hope our study will provide auxiliary strategies and methods for the early prevention of schistosomiasis japonica.