INTRODUCTION: Nanotechnology has been greatly utilized for bone regeneration strategies. It helps overcome some of the current limitations associated with bone regeneration methods Propolis is a natural substance made by the honeybee, it has effective antioxidant, antimicrobial, and anti-inflammatory effects. Moreover, it has multiple biological effects including improvement of wound healing and bone regeneration. OBJECTIVES: comparison of the effectiveness of NanoBone graft and propolis material on the inter-radicular bone regeneration in Mongrel dogs. MATERIALS AND METHODS: A split mouth design was carried out using the third and fourth mandibular premolars of 3 healthy mongrel dogs. A total of 12 grade II furcation defects were surgically created. The defects in the right side were treated with NanoBone graft and then a collagen membrane was used to cover the defects. In the left side the defects were treated with propolis and then covered with collagen membrane. The dogs were sacrificed after 4 weeks. Segments of the jaw bone containing the defects were then dissected out and prepared for histological evaluation. RESULTS: Both percentage of bone fill and percentage of bone surface area in defects treated with propolis powder were higher than those in NanoBone-filled defects. CONCLUSIONS: Both propolis and NanoBone graft materials have bone regenerative effects with higher ability of propolis to regenerate bone.