Background: In this study, we evaluated the effect of periodontal splints made from different materials on the stress distributions in compromised periodontal tissues and cement layers, using a computer simulation of mastication. Methods: Twenty-five 3D models were created for a segment of mandibular teeth with different periodontal splints bilaterally extended to the canines. The models were divided into five groups according to the different materials and thicknesses (mm) of the splints: the non-splinted group, PEEK 0.7 group, PEEK 1.0 group, FRC group, and titanium group. Each group was subdivided based on five bone loss levels. Tooth 41 of each model was subjected to vertical and oblique (θ = 45°) static loads of 100 N, respectively, onto the incisal edge. The von Mises stresses and maximum principal stress were analyzed using Abaqus software. Results: Oblique loading resulted in higher stresses on periodontal tissues, cement layers, and splints than those caused by vertical loading. The lower the supporting bone level, the greater the stress difference between the splinted groups and the non-splinted group. In model 133,331, with severe bone loss, the maximum von Mises stress values on the alveolar bone in tooth 41 under oblique loading dramatically decreased from 406.4 MPa in the non-splinted group to 28.62 MPa in the PEEK group and to 9.59 MPa in the titanium group. The four splinted groups presented similar stress distributions in periodontal tissues. The lowest stress level on the splint was observed in the PEEK 0.7 group, and the highest stress level was transferred to the cement layer in this group. Stress concentrations were primarily exhibited at the connectors near the load-carrying area. Conclusions: The tested splinted groups were all effective in distributing the loads on periodontal tissues around splinted teeth with similar patterns. Using splinting materials with low elastic moduli reduced the stress concentration at the splint connectors, whereas the tensile stress concentration was increased in the cement layer. Thus, the use of adhesive cement with a higher elastic modulus is recommended when applying less rigid PEEK splints.