This paper presents two-degree-of-freedom (2-DOF) robust loop-shaping control methodology to stabilize a reverse osmosis (RO) desalination system operating under significant uncertainties, external disturbances and measurement noises, and to reduce product water cost. This method has the advantages that no information about the plant uncertainty is required and it can deal with external disturbance and noise simultaneously. The controlled RO plant is a multi-input multi-output (MIMO) system. The two controlled variables are product water flow and product water salinity, which are fundamental in water desalination. The result shows that the achieved controller has very good performance which can deal with up to 52% uncertainty, and eliminate 60% of disturbance and 70% of noise, while common existing controllers in RO desalination can't cover the uncertainty and disturbance or can only deal with small values of these factors. Now that the software and hardware in the RO plant are sufficiently robust, it is possible to use this powerful method for better water quality control of RO systems.