Using a three-dimensional finite element analysis, this study aimed to evaluate the effect of different cements’ thicknesses and Poisson’s ratios on the stress distribution in enamel, dentin, restoration, and resin cement in a computer-aided design of a class II disto-occlusal cavity. Dental tomography was used to scan the maxillary first molar, creating a three-dimensional tooth model. A cavity was created with a 95 degree cavity edge angle. Resin cement with varying Poisson’s ratios (V1: 0.35 and V2: 0.24) was used under the amalgam. The simulated groups’ thicknesses ranged from 50 µm to 150 µm. A load of 600 N was applied to the chewing area. The finite element method was used to assess the stress distribution in the enamel, dentin, restorations, and resin cement. The stress in the restoration increased with the use of a 100 µm resin cement thickness and decreased with the use of a 150 µm resin cement thickness. For the V1 and V2 groups, the cement thickness with the maximum stress value for the enamel and dentin was 150 µm, while the cement thickness with the lowest stress value was 50 µm. The greatest stress values for V1 and V2 were obtained at a 150 µm cement thickness, while the lowest stress values were observed at a 100 µm cement thickness. Using resin cement with a low Poisson’s ratio under amalgam may reduce stress on enamel and restorations.