Bone tissue engineering offers a potential alternative to conventional grafting by combining biocompatible scaffolds with biological stimulants. Polycaprolactone (PCL) is a biodegradable polyester with good mechanical strength and biocompatibility. Hydroxyapatite (HA) is a calcium phosphate mineral that is a major component of bone and has excellent bioactivity and biocompatibility. This research investigated the histopathological effects of PCL-HA nanocomposite scaffolds along with their combination with platelet-rich fibrin (PRF), on the regeneration of bone in rabbit calvarial bone defects. Four circular full-thickness bone defects of 5.00 mm in diameter were created on the calvarial bone of 15 male New Zealand white rabbits. Three defects were filled with PRF, PCL-HA, and PCL-HA/PRF, and one defect was served as a control with no filler. Histopathological evaluations were conducted at 4-, 8-, and 12-weeks post-implantation. Data were evaluated using the Kruskal-Wallis and Mann-Whitney U tests. Significant differences were observed between the treatment and control groups regarding bone regeneration throughout all 12^th weeks studied. In the 4^th weeks, no significant differences in bone regeneration were noted among the treatment groups. In the 8^th weeks, most new bone formation was observed in the PCL-HA/PRF group. Both the PCL-HA and PCL-HA/PRF groups significantly improved bone regeneration compared to the control and PRF groups, with the PCL-HA/PRF group demonstrating the greatest bone formation, and vascularization and the lowest inflammation by the 12^th week. Thus, PCL-HA/PRF could be considered as a suitable alternative to bone grafts and could be increasingly utilized in orthopedic surgery and bone tissue engineering.