Patients suffering from motor disorders or weakness resulting from either serious spinal cord injury or stroke often require rehabilitation therapy to regain their mobility. In the lower limbs, exoskeletons have two motors aligned with the patients’ hip and knee to assist in rehabilitation exercises by supporting the patient’s body structure to increase the torques at the hip and knee joints. Assistive rehabilitation is, however, challenging, as the human torque is unknown and varies from patient to patient. This poses difficulties in determining the level of assistance required for a particular patient. In this paper, therefore, a modified extended state observer (ESO)-based integral sliding mode (ISM) controller (MESOISMC) for lower-limb exoskeleton assistive gait rehabilitation is proposed. The ESO is used to estimate the unknown human torque without application of a torque sensor while the ISMC is used to achieve robust tracking of preset hip and knee joint angles by considering the estimated human torque as a disturbance. The performance of the proposed MESOISMC was assessed using the mean absolute error (MAE). The obtained results show an 85.02% and 87.38% reduction in the MAE for the hip and joint angles, respectively, when the proposed MESOISMC is compared with ISMC with both controllers tuned via LMI optimization. The results also indicate that the proposed MESOISMC method is effective and efficient for user comfort and safety during gait rehabilitation training.