In a preliminary study, Lactobacillus plantarum C29 was found to suppress 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice. Therefore, to understand whether an anti-colitic probiotic C29 could attenuate memory impairment, we examined the effects of C29 on TNBS-induced memory impairment in mice. Orally administered Lactobacillus plantarum C29 attenuated TNBS-induced memory impairment in mice in the Y-maze, noble object, and passive avoidance task tests. C29 treatment increased TNBS-suppressed hippocampal brain-derived neurotrophic factor expression and inhibited TNBS-induced hippocampal NF-κB activation and blood LPS levels. Moreover, C29 restored the TNBSdisturbed gut microbiota composition. These findings suggest that C29 can alleviate memory impairment presumably by restoring the gut microbiota composition.