Bone healing is still a great challenge in orthopedic surgery and clinical practice. There is a dearth of research investigating the effect of Zeolite/Collagen (ZC) nanocomposite on bone regeneration. In the present study, a critical segmental defect of the rabbit femur was repaired using defects in femurs repaired by ZC nanocomposite, and the effects were examined histologically. In total, 45 rabbits at seven months of age weighing 3.5 kilograms were utilized in this study. After making the bone defects, all animals were randomized into three groups (n=15). In a normal control group (NC), a defect was created, no intervention was made, and the skin incision was sutured. On the other hand, in the ZC group, the nanocomposite of ZC was placed into the created defect. In the hydroxyapatite group (HA), the hydroxyapatite was placed into the created defect. The samples were collected on days 15, 30, and 45 postoperatively and assessed histopathologically. The mean scores of the index of the union were compared and considerable alterations were observed in this regard in the experimental groups (P<0.05). The values of the index of spongiosa demonstrated that on day 15, it was the highest in the ZC group (2.2) and lowest in the HA and NC groups (0.6). Moreover, the values of the index of bone marrow demonstrated no noticeable alteration among the values of the index of bone marrow in the experimental groups (P>0.05). The findings of this study demonstrated that ZC nanocomposite might be considered for reconstruction in bone damages. It seems the ZC nanocomposite bears a crucial capability in the reconstruction of bone damages and might be used as a biological frame in bone damages.