Topically applied chlorhexidine and hyaluronan have many studies supporting their use to enhance oral wound healing. Allantoin is widely used topically to promote epithelial proliferation and wound healing, with very little scientific evidence to support such uses. This study investigated and compared the influence of these agents on the healing of intra-oral excisional wounds with large epithelial and connective tissue defects.Excisional wounds, 3 mm in diameter, were made at the centre of the palate of 125 Wistar male albino rats. Five animals constituted the baseline group at time 0. The remaining animals were divided into four experimental and one control groups, in which chlorhexidine digluconate gel 0.2% (Perio.Kin®), hyaluronan gel (Gengigel®), allantoin 0.5% in vehicle gel, vehicle gel alone and nothing were applied daily to the wounds. The wound areas were measured photographically and the epithelialization rates were determined histologically at 0, 3, 7, 14 and 21 days post-surgery.The mean wound area and mean distance between the epithelial margins decreased significantly with time in all experimental and control groups (P < 0.05). A significant rate of wound area reduction was observed following the use of Perio.Kin® and Gengigel® at 7 and 14 days. Perio.Kin® showed a significant rate of wound epithelialization at 7 days. Allantoin did not positively or negatively affect wound healing.None of the tested agents had a negative effect on the rate of wound healing when applied on an excisional wound with epithelial and connective tissue defect. Positive results were achieved with Perio.Kin® and Gengigel®.