The aim of this study was to investigate the effect of benzydamine hydrochloride bioadhesive gel on healing of oral mucosal ulceration in an animal model. For in vivo determination of the effects of the bioadhesive gel, 36 rabbits were separated into three groups: the first group was treated with the gel formulation without active agent, the second group with the gel formulation containing benzydamine, and the third group received no treatment. Clinical healing was established by measuring the area of the ulcer in each test group on days 3, 6, 9 and 12. Histological healing was determined on the same days. Benzydamine containing gel applications resulted in a decrease in the ulcer area in 12 days (p = 0.000). Histological evaluation showed that the benzydamine group had a higher mean histological score than the base and the control groups during the whole test period, and the difference between the benzydamine group and the control group was significant (p = 0.04). The bioadhesive gel formulation of benzydamine hydrochloride showed a statistically significant increased rate of mucosal repair in this experimental standard mucosal wound animal study. It is a candidate for the topical treatment of oral mucosal ulcerative lesions.