In this paper, the method for compensating the temperature drift of high-G MEMS accelerometer (HGMA) is proposed, including radial basis function neural network (RBF NN), RBF NN based on genetic algorithm (GA), RBF NN based on GA with Kalman filter (KF), and the RBF NN + GA + KF method compensated by the temperature drift model. First, this paper introduces an HGMA structure working principle, conducts a finite element analysis, and produces the results. The simulation results show that the HGMA working mode is the 1st order mode, and its resonant frequency is 408 kHz. The 2nd order mode resonant frequency is 667 kHz, and the gap with the first mode is 260 kHz, indicating that the coupling movement between the two modes is tiny, so the HGMA has good linearity. Then, a temperature experiment is performed to obtain the output value of HGMA. The output values of HGMA are analyzed and optimized by using the algorithms proposed in this paper. The processing results show that the RBF NN + GA + KF method compensated by the temperature drift model achieves the best denoing consequent. The processing results show that the temperature drift of the HGMA is effectively compensated. The final results show that acceleration random walking improved from 17130 g/h/Hz0.5 to 765.3 g/h/Hz0.5, and bias stability improved from 4720 g/h to 57.27 g/h, respectively. The results show that after using the RBF NN + GA + KF method, combined with the temperature drift model, the temperature drift trend and noise characteristics of HGMA are well optimized.