Alloplastic material has been suggested to reconstruct the alveolar cleft to reduce surgery time, providing an abundant quantity of bone, and no need for the donor site. Platelet-rich fibrin has many growth factors effective in bone healing and tissue maturation. Evaluation of the effectiveness of the application of osteon II collagen with platelet-rich fibrin on the bone healing process in unilateral alveolar cleft patients. This study included 15 patients aged from 7to12 years, with a unilateral alveolar cleft. Osteon II collagen bone substitute with Platelet-rich fibrin membrane was used to reconstruct the alveolar defect. Postoperative density and buccopalatal thickness of Osteon II collagen bone substitute were assessed by cone-beam computerized tomography at immediate postoperatively,6, and 12months after surgery. The density and buccopalatal thickness of Osteon II collagen bone substitute increased after 6 months postoperatively, while it's highly significant increased after 12months, also valuable bone continuity was observed in all patients. We concluded the osteon II collagen bone substitutes with PRF have a regenerative effect, decrease bone substitutes resorption that leads to preserving the volume with increased bone substitutes density. Also, the PRF was used to accelerate the speed of bone formation and to reduce bone resorption.