The problem of designing an observer-based fault-tolerant control allocation mechanism for a multi-input multi-output (MIMO) uncertain descriptor system (DS) subjected to actuator faults/failures and external uncertainties is discussed in this paper. The proposed approach guarantees system performance and closed-loop stability using the integral sliding mode control (ISMC) and a fixed control allocation (CA) strategy. A robust sliding mode observer (SMO) is designed to estimate the states of the DS in a realistic setting. The sliding surface is constructed with the estimated states, following the ISMC principle. To meet the admissibility conditions of DS, a multivariable super-twisting sliding mode control (STSMC) algorithm is designed. The CA technique reallocates the control effort to the remaining healthy actuators on the occurrence of any fault/failure. Lyapunov-based stability is established for the closed-loop system with the controllerâobserver pair. Finally, the proposed design is validated by evaluating various actuator fault/failure situations.