Aim: The aim of this study was to evaluate the clinical and radiographic effect of both Ozone gel and Hyaluronic acid after enucleation of mandibular odontogenic cysts. Subjects and methods: 24 patients complained of an odontogenic cystic lesion in mandible classified into three groups, Group I (Ozone group): Included 8 patients with odontogenic cysts treated by Enucleation followed by Ozone gel application in the surgical cavity. Group II (HA group): Included 8 patients with odontogenic cysts treated by Enucleation followed by Hyaluronic acid application in the surgical cavity. Group III ( Control group): Included 8 patients with odontogenic cysts treated by Enucleation only. Postoperative one-month panoramic view, 3, 6 cone-beam C.T as the radiographic follow-up. Facial edema, pain, and trismus were the clinical parameters at 1,3 and 7 days. Results: The study showed a significant increase in the bone density of both group I (ozone), II (Hyaluronic acid) than the control group comparing the percentage of bone density to the contralateral bone, it was for group I (Ozone group) 45.8%, 69% at follow up of 3,6, months. In group II ( HA ) it was for 51.9%, 72% at follow up of 3, 6, months. It was for group III (control group) 32.6%, 56.1% at follow up of 3, 6, 9 months as there was high statistical significance between-group I, II in comparing with the group I with P-value = 0.04,0.05..Conclusion: Both ozone gel and Hyaluronic acid can be considered to enhance bone regeneration after cystic enucleation due to their specific antimicrobial, anti-inflammatory properties, and increasing angiogenesis in the post-surgical cavities.