Honey, curcumin, ginger, and Nigella sativa are known for their antioxidant, immune stimulation properties, and wound healing effects. This study was conducted to determine the effect of these compounds and their mixture on the bone healing of the radial bone defect model in rats. One hundred and ten radial bone defects in 55 healthy male rats were randomly divided into 11 groups (10 rats per group). Groups 1-5 received honey, curcumin, ginger, and Nigella sativa orally by gavage, and groups 6-10 received the same materials locally by rubbing them on the sutured skin. The bone repair effects of these materials were evaluated by histopathology and biomechanical examinations. Using honey, curcumin, ginger, and Nigella sativa exhibited a beneficial effect to promote bone healing in this study. The biomechanical and histopathologic evaluations showed that the honey (oral), the mixture of honey and curcumin (oral), and the mixture of honey and Nigella sativa (topical) groups exhibited significantly better results on the 52nd postoperative day compared to the other groups.