In this research, 2205/Q235B clad plates were prepared by a vacuum hot rolling composite process. The effects of adding Fe, Ni, and Nb interlayers on the bonding interface structures and the shear strengths of the clad steel plates were studied. The results showed that 2205 duplex stainless steel and the three interlayers produced a large amount of plastic deformation and low-angle boundaries, and the main structures were the recrystallized and deformed grains. There were many recrystallized grains in the microstructure of the Q235B low-carbon steel due to the low deformation in the rolling process. The Fe interlayer had better wettability with the two kinds of steel, but the lower strength led to the reduction of shear strength by about 14 MPa compared with the original clad steel plate. The C element in the Q235B low-carbon steel easily diffused into the Fe interlayer, and the clad steel plate attained a poor corrosion resistance because a large decarburization area was formed. The Nb interlayer reacted with the Mo element in the 2205 duplex stainless steel to form an Nb-Mo binary alloy, which generated long-banded ferrite. The decarburization area was also produced because the Nb reacted with the C element in the Q235B to form hard and brittle NbCx. As a result, the shear strength was significantly reduced by about 282 MPa, and the corrosion resistance of the bonding surface was deteriorated. The Ni interlayer did not react with the alloy elements in both sides, and therefore effectively prevented element diffusion and improved the corrosion resistance of the bonding surface. Due to the low strength of the Ni interlayer and the increased number of bonding surfaces of the clad steel plates, the shear strength was reduced to some extent (about 40 MPa), but it still met the engineering application standards.