In recent years, multi-material design concept has been applied to many industries. Among various methods of joining dissimilar materials, adhesive bonding is quite suitable for the purpose of lightening the weight. In order to choose the most preferable adhesive for improvement of the strength, it is necessary to understand the failure criteria of adhesives. Experiments using pipe specimens with inclined surfaces bonded by an epoxy adhesive were performed, which can achieve multiaxial stress states while solely recurring to a uniaxial tensile test. The failure function of the epoxy adhesive, expressed by the mean stress and octahedral shear stress, was then obtained from the experiment data and compared with that of the acrylic adhesive in the previous research. The failure functions of both adhesives were then applied to the shape optimization of the adhesive layer under different loading conditions. The optimization object is to improve the strength of bonded structures. The optimal shape for different loading conditions differs for each adhesive because of the driving force due to the applied stress. Thus, the final shapes are numerically optimized to attain the highest mechanical integrity of the adhesive layer and show strong dependences on the initial shapes prior to optimization.