The purpose of this study was to histologically evaluate the effects on bone healing of nigella sativa seed extract applied on calvarial defects in an ovariectomized rat model. The study included 32 female rats weighing 280 to 310 g with an average age of 3 months. A defect was created with a trephine burr on each rat calvarium. The rats were divided into 2 groups (control and study) of 8 animals each. All the defects were grafted with a gelatin sponge mixed with normal saline. In the study group, nigella sativa seed extract was applied systemically using an oro-gastric tube. Half of the animals in each group were sacrificed after 2 weeks, and the others after 4 weeks. In the control groups, the defects were not completely filled with regenerated bone. Osteoblast cells were observed more in the study groups. A higher rate of osteoclasts was determined in the control groups. In addition, the nigella sativa group had a statistically greater amount of bone formation than the others group at both 2 weeks and 4 weeks (P <0.05). The systemic application of nigella sativa seed extract demonstrated incredibly positive effects on enhanced bone healing in this experimental osteoporotic model.