Complementary and alternative medicine approaches are gaining ground in everyday practice. Propolis is a bee product that has been suggested to have bone regenerative effects. This study was conducted to compare the effectiveness of Egyptian propolis with nanohydroxyapatite graft on furcation defect regeneration in mongrel dogs. A split mouth design was utilized in six clinically healthy mongrel dogs. A total of 24 Class II furcation defects were surgically created in mandibular third and fourth premolars. The defects on the right side were filled with nanohydroxyapatite graft and covered with collagen membrane, while on the left side the defects were filled with propolis and also covered with collagen membrane. The dogs were sacrificed after 1 and 3 months. Segments containing the defects were prepared for histological evaluation. The histological evaluation after one month revealed newly formed bone in both treatment groups. However, after 3 months, the bone trabeculae appeared thinner in the collagen/nanohydroxyapatite group than in the collagen/propolis group. The histomorphometric evaluation showed a significant increase in bone height as well as bone surface area for the collagen/propolis group compared to collagen/nanohydroxyapatite group. Both Egyptian propolis and nanohydroxyapatite graft material showed favorable periodontal regenerative effect. Propolis showed increased cellular proliferative ability that could be beneficial in reducing the healing period needed after periodontal therapy.