Inflammatory bowel diseases (IBD) are idiopathic diseases of the gastrointestinal tract characterised by recurrent inflammation that require lifelong treatments. It has been shown that certain strains of lactic acid bacteria (LAB) can produce specific health-promoting compounds in foods or in the gastrointestinal tract that can in turn prevent and/or treat IBD. This study was designed to evaluate the possible therapeutic potential of soymilk fermented by the riboflavin-producing strain Lactobacillus plantarum CRL 2130 in a trinitrobenzene sulfonic induced colitis mouse model. Mice that received soymilk fermented by L. plantarum CRL 2130 showed a decrease in weight loss, lower damage scores in their large intestines, lower microbial translocation to liver and decreased cytokines levels in their intestinal fluids compared to animals that received unfermented soymilk or soymilk fermented by a non-riboflavin-producing L. plantarum strain. This is the first report that demonstrates that a riboflavin-producing LAB was able to prevent experimental colitis in a murine model.