In summary, our results suggest that gastrodin could significantly ameliorate colitis in mice by enhancing the expression of mucin, E-cadherin, and tight junction protein occludin, attenuating the inflammation-related NF-κB signaling pathway, alleviating oxidative stress, and inhibiting the expression of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6. Here, MUC5AC is linked to colitis.