A novel composite three-dimensional (3D) guidance law based on an adaptive integral sliding mode (AISM) control utilizing a nonlinear disturbance observer (NDOB) technique is proposed for missiles. First, an integral sliding mode control is selected as the guidance law to get rid of the reaching phase of sliding mode control. Second, the switching gains are adjusted by designing an adaptive law. Finally, the NDOB is designed to estimate and compensate for the unknown target accelerations that are considered as the disturbance. Thus the NDOB and AISM law are combined into a novel composite guidance law to improve performance and to reduce the chattering phenomenon. Finally, to verify the effectiveness and robustness, numerical simulations are performed in different scenarios and these results are presented comparatively with the augmented proportional navigation (APN) and the AISM guidance law. Moreover, the proposed law outperforms the other schemes regarding the miss distance and interception time.