Polycaprolactone (PCL) is a suitable material for bone repair due to good biocompatibility and mechanical properties. However, low bioactivity and hydrophobicity pose major challenges for its biomedical applications. To overcome these limitations, PCL-based scaffolds loaded with bioactive agents have been developed. Salicin (Sal) is an anti-inflammatory and analgesic herbal glycoside with osteogenic potential. In the present study, we aimed to produce a salicin-laden PCL (PCL-Sal) scaffold for bone healing applications. Three-dimensional (3D) scaffolds were produced and their biocompatibility, and physical-chemical characteristics were determined. The osteogenic potential of the net PCL (nPCL) and PCL-Sal scaffolds was evaluated using bone marrow mesenchymal stem cells (BMSCs). Scaffolds were implanted into a 4-mm bone defect created in the femur of adult rats, and the new bone fraction was determined using micro-CT scanning at one-month follow-up. The PCL-Sal scaffold had a structure, porosity, and fiber diameter suitable for bone construction. It also possessed a higher rate of hydrophilicity and bioactivity compared to the nPCL, providing a suitable surface for the proliferation and bone differentiation of BMSCs. Furthermore, PCL-Sal scaffolds showed a higher capacity to scavenge free radicals compared to nPCL. The improved bone healing potential of the PCL-Sal scaffold was also confirmed according to in vivo implantation results. Our findings revealed that the salicin-laden implant could be considered for bone repair due to desirable characteristics of salicin such as hydrophilicity, surface modification for cell attachment, and antioxidant properties.