Computer-aided design/manufacturing (CAD/CAM) endocrowns are commonly applied to strengthen endodontically treated teeth with too much tissue loss. Monolithic or multilayer structures may be used for this purpose. Restorations made with multilayering technique may mimic natural teeth better. The purpose of this finite elemental analysis (FEA) research was to appraise the impact of different materials and application methods on the stress effect in CAD/CAM applied endocrowns. A 3-dimensional mathematical model simulating an endodontically treated mandibular first molar was modeled. The sample was then modified to imitate the ceramic endocrown applied molar tooth. Three FEA models were then created from this main model to simulate the following endocrown structures: 1: lithium disilicate reinforced glass ceramic, 2: monolithic zirconia, 3: multi-layered glass ceramic and glass-fiber endocrown (the core structure was composed of glass-fiber while the crown is prepared by glass ceramic). The SolidWorks/CosmosWorks programs were used as structural analysis programs. The materials used in the study were accepted as homogeneous and isotropic. A 300 N load was applied to the occlusal surfaces of the restored teeth. The results of the study are presented according to the von Mises criteria. The von Mises stresses recorded at the cavity base were 0.417–0.7, 0.6–0.85, and 0.083–0.25 MPa, respectively. The multilayering technique reduced stresses as compared to the other two different designs and materials and showed similar stress distributions with the natural tooth model. Models simulating teeth with a zirconia endocrown showed the highest stresses. The multilayering technique using fiber-reinforced glass ceramic as a core and glass ceramic as a crown reduced the stresses and showed stress distributions similar to natural teeth. This technique can be used to create biomimetic restorations with a core material, which mimics dentin (glass-fiber reinforced ceramic) and crown material, which mimics enamel (glass ceramic).