Introduction: Bone remodeling after enucleation of odontogenic mandibular cysts represents a challenging sequela in the maxillofacial area. Ozone therapy and Hyaluronic acid are considered to be future modalities in enhancing bone healing in extended surgical defects. Aim of the study: The of this study was to evaluate the clinical and radiographic effect of both Ozone gel and Hyaluronic acid after enucleation of mandibular odontogenic cysts. Patients and Methods: 24 patients complained of an odontogenic cystic lesion in mandible classified into three groups, each group included 8 patients with odontogenic cysts treated by Enucleation and according to the graft material into :Group I (Ozone ),Group II ( HA group):, Group III ( Control group). 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. 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.