Lightweight structures as sandwich panels are one of the innovation products to drive the future of the wood/plywood industry for the near future. Material consumption, thus environmental impact, is the driving factor to replace commonly used plywood panels with the plywood sandwich structures. The aim of this paper is to elaborate the design methodology for different core type plywood sandwich panels under the flexural loading. The methodology is based on sampling of the numerical experiments by the finite element code ANSYS and approximation of the response values of the four point bending tests. This methodology is a collection of mathematical and statistical techniques that are useful for the modelling and analysis of problems in which structural responses are influenced by several variables and the objective is to optimize these responses. The methodology is often referred to as metamodelling as they provide a model of a model, replacing the expensive simulation analyses during the optimisation process. Moreover, validations of metamodelling procedure for design of I-core sandwich panels with physical tests have been evaluated. The sandwich panels used in physical experiments were made of plywood outer plate and I-core filling strips and the bending properties have been tested according to EN 789. The structural flexural stiffness capacity and weight efficiency have been elaborated for the I-core sandwich panels by the metamodelling procedure. The design guidelines have been elaborated and validated with the physical experiments.