Summary: Solving fourth or higher order differential equations using localized numerical methods as the finite element, the finite difference and the localized radial basis functions (LRBFs), show difficulties to get accurate results. So many authors adopted iterative methods to deal with biharmonic equation by decoupling it into two Poisson’s problems. In this paper we investigate the formulation of a mixed fourth order boundary value problem as an optimal control one. Then, we establish a new iterative method by coupling an optimization iterative scheme and localized radial basis functions meshless collocation method to deal with the numerical solution of such problem. To transform the problem into an optimal control one, we firstly construct the constraints functions by splitting the biharmonic equation into two coupled Laplace equations. The Neumann boundary condition is used as energy-like error functional to be minimized. Theoretical analysis of the existence and uniqueness of the solution of such formulated optimization problem and its equivalence to the initial biharmonic problem are also demonstrated. Finally we show the effectiveness of the proposed method by solving problems in both convex and non-convex regular and irregular domain.