Objective To investigate the effect of interlocking intramedullary nailing for fracture nonunion on bone metabolism. Methods From May 2018 to March 2023, a total of 60 patients with nonunion after lower limb fracture were randomly divided into two groups, with 30 cases in each group. The control group was treated with dynamic compression plate internal fixation, and the experimental group was treated with interlocking intramedullary nail fixation. Both groups were additionally treated with nerve growth factor. The time of callus appearance and the time of fracture healing were recorded, and clinical efficacy was evaluated. The serum levels of type Ⅰ collagen β C-terminal cross-linked telopeptide （β-CTX）, osteocalcin （BGP）, and type Ⅰ procollagen N-terminal propeptide （PINP） were detected before and after treatment. Results Compared with the control group, the callus appearance time and fracture healing time in the experimental group were significantly shortened （P<0.05）. The excellent and good rate of treatment of the experimental group （86.67%） was significantly higher than that of the control group （56.67%） （P<0.05）. Before treatment, there was no significant difference in bone metabolism indexes between the two groups. After treatment, the changes of bone metabolism indexes in the two groups showed improved osteogenesis compared with that before treatment （the level of β-CTX was reduced, and the levels of BGP and PINP were increased） （P<0.05）; in addition, the level of β-CTX in the experimental group was significantly lower and the levels of BGP and PINP were significantly higher in the experimental group than those in the control group （P<0.05）. Conclusion In the treatment of fracture nonunion, the use of interlocking intramedullary nailing can not only reduce postoperative functional recovery time and complications, but also relieve pain and improve the ability of daily living, which is worthy of recommendation.