Gastric ulcers are among the major GIT problems impacting people globally. A number of natural compounds have been evaluated for gastric ulcer treatment. One of the most popularly used medicinal plants is Aloe vera, which has powerful anti-inflammatory and healing actions. Pantoprazole was used as a reference drug. The current investigation is intended to determine the therapeutic benefits of Aloe Vera in gastric ulcers triggered by ethanol in rats and to clarify if Aloe Vera achieves its therapeutic benefits by improving mucosal immunity through modulating MyD88 expression. Rats were divided into four groups: normal control, ethanol, ethanol + Aloe Vera, and ethanol + Pantoprazole. Gastric ulceration was triggered by giving only a single dose of 100% ethanol (5 ml/kg b.w.t.) orally. Aloe Vera and Pantoprazole were given orally for 2 weeks. At the end of the experiment, after rat sacrificing and stomach harvesting, macroscopic, molecular, and histopathological evaluations were done. The results revealed that the stomach mucosa in the ethanol group developed a severe ulcerative lesion. Also, myeloid differentiation primary response protein 88 (MYD88) gene expression was significantly upregulated. The ethanol group's histopathological examination revealed severe epithelial damage, inflammation, and edema. The macroscopic mucosal lesion, molecular alterations, and histopathological abnormalities are all alleviated by Aloe Vera treatment. Aloe Vera is more significant than medical treatment with pantoprazole. Finally, we concluded that Aloe Vera's ability to mitigate stomach ulcers is through its anti-inflammatory and healing capacities. Thus, Aloe Vera could potentially be utilized as a medication for relieving gastric ulcers.