The dome structure is suitable as a roof for large spatial structures because it can maintain the shape without installing columns in the internal space. However, the structure characteristics of the lower and upper structures of the dome structure are different, and damage may occur when an earthquake occurs. Therefore, in this study, mid-story isolation system was applied to the ribbed dome and geodesic dome structures to analyze the seismic response of the lower and upper structures according to the dome shape. As a result of the analysis, the displacement of the ribbed dome increased, but the deformation of the ribbed dome and the response of the lower structure decreased, and the seismic response of the geodesic dome decreased overall. From this result, the effect of the isolator according to the shape of the dome structure was confirmed, and the mid-story isolation is considered effective in reducing the seismic response of the upper and lower structures.