Underwater vehicle-manipulator system (UVMS) is a commonly used underwater operating equipment. Its control scheme has been the focus of control researchers, as it operates in the presence of lumped disturbances, including modelling uncertainties and water disturbances. To address the nonlinear control problem of the UVMS, we propose a robust optimal control approach optimized using grey wolf optimizer (GWO). In this scheme, the nonlinear dynamic model of UVMS is deduced to a linear state-space model in the case of the lumped disturbances. Then, the GWO algorithm is used to optimize the Riccati equation parameters of the H∞ controller in order to achieve the H∞ performance criterion, such as stability and disturbance rejection. The optimization is performed by evaluating the performance of the closed-loop UVMS in real-time comparison with the popular artificial intelligent algorithms, such as as ant colony algorithm (ACO), genetic algorithm (GA), and particle swarm optimization (PSO), using feedback control from the physical hardware-in-the-loop UVMS platform. This scheme can result in improved H∞ control system performance, and it is able to ensure that UVMS has strong robustness to these lumped disturbances. Last, the validity of the proposed scheme can be established, and its performance in overcoming modeling uncertainties and external disturbances can be observed and analyzed by performing the hardware-in-the-loop experiments.