ABSTRACT Intestinal microﬂora and inﬂammation are associated with the risk of inﬂammatory bowel diseases. Noni (Morinda citrifolia L.) has various bioactivities, but its effect on colon health remains unknown. This study focused on the effects of fermented noni fruit extracts on colon microﬂora and inﬂammation of colon epithelial cells. The anti-inﬂammatory activities of ethanol and ethyl acetate extracts on Caco-2 cells were evaluated including interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2). The growth of Lactobacillus and Biﬁdobacterium species was promoted by ethanol extract. Ethyl acetate extract decreased intracellular reactive oxygen species and signiﬁcantly suppressed COX-2, IL-8, and prostaglandin E2 production and neutrophil chemotaxis by suppressing the translocation of the p65 subunit. Quercetin was the main contributor to the anti-inﬂammatory activity. The fermented noni fruit promoted probiotic growths and downregulated the intracellular oxidation and inﬂammation in Caco-2 cells. These results suggest that fermented noni fruit might protect against inﬂammatory diseases of the colon.