This paper investigates the autocalibration of microelectromechanical systems (MEMS) triaxial accelerometer (TA) based on experimental design (DoE). First, for a special 6-parameter second-degree model, a six-point experimental scheme is proposed, and its G-optimality has been proven based on optimal DoE. Then, a new linearization approach is introduced, by which the TA model for autocalibration can be simplified as the expected second-degree form so that the proposed optimal experimental scheme can be applied. To reliably estimate the model parameter, a convergence-guaranteed iterative algorithm is also proposed, which can significantly reduce the bias caused by linearization. Thereafter, the effectiveness and robustness of the proposed approach have been demonstrated by simulation. Finally, the proposed calibration method has been experimentally verified using two typical types of MEMS TA, and desired experimental results effectively demonstrate the efficiency and accuracy of the proposed calibration approach.