Food mediates susceptibility to inflammatory bowel diseases (IBDs) associated with the microbiome. Existing studies suggest that a high-sugar and high-fat diet promotes IBDs, but whether a plant-based diet is fully harmless to IBD improvement remains unknown. In this study, for the first time, we assessed the effect of soybean and its carbohydrates on dextran sodium sulfate (DSS)-induced colitis. In a DSS-induced colitis mouse model (BALB/C WT), the oral administration of soybeans worsened colitis, which was associated with higher disease activity index, histology score and expression of pro-inflammatory cytokines, and lower expression of anti-inflammatory cytokines. Here, 16S rRNA sequencing and elimination of gut bacteria by antibiotics showed that the exacerbating colitis caused by soybeans depends on the changes in the intestinal flora. Furthermore, the gavage of soybean carbohydrates such as sucrose and raffinose-family oligosaccharides altered the intestinal microbiota and worsened inflammation. When co-cultured with macrophages (RAW 264.7), the metabolites of the disordered intestinal flora, isolated Escherichia coli and purified LPS showed high macrophage toxicity to inhibit pathogen clearance. These results indicate that the intake of soybeans and soybean carbohydrates is not conducive to recovery from IBDs based on changes in gut microbiota and metabolites affecting the activities of macrophages.