A bone defect is the effect of either injury or disease; it can be repaired due to the natural ability of bones. In the healing process, it needs an active substance modulating its immunology process. Mesenchymal stem cells (MSCs) secretome will be one of the promising therapies in the future since it is a cell-free therapy. As of today, research exploring the potential of use of MSCs secretome in tissue engineering is rare. MSCs secretome’s properties are better than MSCs itself because they consist of so many growth factors, cytokines-chemokines, and transcription factors which accelerate bone defect healing. This review was to describe the composition of MSCs secretome as a stimulator candidate in bone healing process. It also warrants further investigation of the use of MSC secretome in injured bone healing.