Gastric ulcers (GUs) are superficial diffuse lesions of the gastric mucosa that are characterised by being vulnerable to infection, difficult to cure and liable to recur. Bletilla ochracea Schltr. (BO) has the effects of astringent hemostasis, muscle growth and pain relief. We examined the effects of BO on acute GUs and their potential mechanisms from the perspectives of inflammation, oxidative stress and gut microbiota. Results indicated that BO alleviated pathological injury to the gastric mucosa and markedly alleviated oxidative stress and inflammation. In addition, BO significantly upregulated the levels of Nrf2, HO-1, NQO1 protein, and downregulated the levels of NF-κB p65, TLR4 protein. Moreover, BO significantly increased promoting the nuclear transfer of Nrf2 and markedly reduced the nuclear translocation of NF-κB p65. Furthermore, BO effectively modulated gut microbiota by increasing the diversity of species and relative abundance. Our study provided evidence that BO alleviated ethanol-induced acute GUs by activating the Nrf2/HO-1 and inhibiting the NF-κB p65/TLR4 signalling pathway, regulating dysbiosis of gut microbiota.