Background: Areca nut (Areca catechu Linn.) is the seed of the fruit of the oriental palm that is commonly used among Southeast Asian communities. Chrysanthemum (Dendrathema grandiflora) is a flowering plant originating from East Asia and dominantly grows in China. Both of these plants have strong antioxidant activities. To investigate the mechanism of their wound healing activities, we prepared areca nut and chrysanthemum polyethylene oral gel and performed several in vivo assays using Sprague–Dawley rats. Methods: Sprague–Dawley rats were divided into six groups: Negative control group (rats with base gel treatment), positive control group (rats treated with triamcinolone acetonide), F1 (treatment with 20% areca nut:80% chrysanthemum), F2 (treatment with 50% areca nut:50% chrysanthemum), F3 (treatment with 80% areca nut:20% chrysanthemum), and normal group (without ulcer and treatment). Traumatic ulcers were performed on the buccal mucosa of all experimental animals that received topical oral gel and triamcinolone acetonide twice a day for seven days. The clinical and histological characteristics were analyzed and scored. Results: During the six days, the ulcerated area receded linearly over time and was completely cicatrized in F2, F3, and the positive control group (Dependent t-test, p<0.05). There were significant increases in body weight in F2 and positive control groups. There were no significant differences between groups in histology examination (Kruskal Wallis test, p<0.05). The moderate score of TNF-α levels was seen in F2 and positive control groups (ANOVA/Tukey test, p<0.05). In the collagenases assay, a high concentration of areca nut (F3) induced the abundance of collagen during the ulcer healing process. Conclusions: The combination of areca nut and chrysanthemum extract in the oral gel can optimize the healing of traumatic oral ulcers in Sprague-Dawley rats through the increase of TNF-α and collagen deposition.