In recent years, the applications of rotating inertial navigation systems (INSs) have been developed rapidly. By controlling the rotation of the inertial measurement unit, the drift error of an inertial device can be modulated and the divergence of INS errors can be suppressed. However, attitude errors and velocity errors accumulate as the result of the scale factor asymmetry of gyros based on a forward–reverse rotating system, which offers better performance than single-axis rotational navigation systems. In this paper, the error mechanism of scale factor asymmetry in forward–reverse rotating systems is discussed in detail. Based on a system-level fitting method, error deduction of the scale factor asymmetry of a gyro under different conditions, including the level and tilt environments, are introduced, respectively. Thus, a self-calibration and compensation method based on scale factor asymmetry is proposed. The simulation and experiment results show that the iterative calibration and compensation method has a positive effect on eliminating scale factor asymmetry, and the precision of initial alignment and navigation can be improved after compensation.