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Six-axis motion is essential for the evaluation of the wear failure modes of dental prostheses with complete teeth morphologies, and a high occlusal force capacity is vital for static clenching and dynamic bruxism. Additionally, the saliva environment influences abrasive particles and crack growth. The present research was aimed at the development of a six-axis masticatory and saliva simulator with these capacities. The masticatory simulator was designed based on a six-axis parallel mechanism, and the saliva simulator consisted of a saliva circuit and a temperature control loop. A control system of the masticatory and saliva simulators was constructed. The operating interface includes a centric occlusal position search, a static test, a dynamic test, a saliva supply, and data reporting. The motion and force performances of the masticatory simulator were evaluated. The flow rate and temperature change of the saliva simulator were calculated. For the occlusal position-searching, the driving amplitude is linear with the moving variables during minor one-axis motion. For the static tests, the force capacity of the driving chain is 3540 N, while for the dynamic tests, the force capacity is 1390 N. The flow rate of the saliva is 0.18–51.84 mL/min, and the saliva can effectively wet the prosthesis without the risk of overflow. Moreover, the saliva temperature can increase from room temperature (23°C) to body temperature (37°C) in about 6 min. The proposed DUT-2 simulator with six-axis motion, high force, and a salvia environment provides an in vitro testing approach to validate numerical simulation results and explain the clinical failure modes of prostheses. The centric occlusal position-searching, static tests, and dynamic tests could therefore be executed using a single testing machine. Moreover, the proposed device is more compact than previously reported six-axis masticatory simulators, including the Bristol simulator and DUT-1 simulator.