Since the number of trans-femoral amputees has increased by industrial or traffic accidents in modern society, the demand for a prosthetic limb has also increased year after year. In this case, loads applied to a prosthetic limb are important indices for contact relation and position relation to the human body. However, conventional systems cannot measure long continuous walking motion of amputees under a wide range of environmental conditions. Moreover, conventional structural optimization method for a multi-axis force/moment sensor has not been put into practical use. In this paper, we developed a six-axis force/moment sensor that can be attached to a prosthetic limb and improved performance of this sensor by a new practical structural optimization method. The developed sensor in the present study can be easily fixed between the artificial knee joint and the prosthetic foot to detect the load condition during walking. We used finite element analysis, response surface method and desirability function as proposed techniques for multi-objective structural optimization in three-dimensional space. As results in the present study, we optimized the structure of this sensor and validated the effectiveness of optimum design variables and the proposed techniques.