The use of mucoperiostial flaps during cleft palate surgery is associated with altered palatal bone growth and development. We analyzed the potential usefulness of a bioengineered oral mucosa in an in vivo model of cleft palate. First, a 4 mm palate defect was created in one side of the palate oral mucosa of 3 week-old New Zealand rabbits, and a complete autologous bioengineered oral mucosa (BOM) or acellular fibrin-agarose scaffold (AS) was implanted. No material was implanted in the negative controls (NC), and positive controls were not subjected to palatal defect (PC). Animals were allowed to grow for 6 months and the results were analyzed morphologically (palate mucosa and bone size) and histologically. Results show that palatal mucosa and bone growth and development were significantly altered in NC and AS animals, whereas BOM animals had similar results to PC and the bioengineered oral mucosa was properly integrated in the host palate. The amount and compaction of collagen fibers was similar between BOM and PC, and both groups of animals had comparable contents of proteoglycans and glycoproteins at the palate bone. No differences were found for decorin, osteocalcin and BMP2. The use of bioengineered oral mucosa substitutes is able to improve palate growth and maturation by preventing the alterations found in animals with denuded palate bone. These results support the potential clinical usefulness of BOM substitutes for the treatment of patients with cleft palate and other conditions in which palate mucosa grafts are necessary with consequent bone denudation.