According to the special shape of a blended-wing-body underwater glider (BWBUG), the cabin-skeleton coupling structure including a pressure cabin structure and a skeleton structure is designed in its internal space, which plays a role of support and pressure resistance. Based on fixed BWB shape parameters, firstly, the pressure cabin structure and skeleton structure were parametrically modeled. Next, finite element analysis (FEA) was conducted for the coupling structure in the hanging before entering the water and deepwater pressure conditions respectively, mainly analyzing the strength, stiffness, and stability. Then, the maximum buoyancy-weight ratio is used as the target, besides, the specific indicators for the obtained strength, stiffness, and stability are used as constraints. Finally, a surrogate-based constrained global optimization algorithm (SCGOSR) is adopted to optimize the coupling structure. After the optimization, the buoyancy-weight ratio is increased by about 43%, and a satisfactory cabin-skeleton coupling structure is obtained.