Interlayer hybrid composites are composed of a variety of fibers and matrix, which enables the full play of advantages of various composites and realizes the coordination of various properties. However, complexity of the manufacturing process and uncertainty of the parameters make it difficult to optimize the design of interlayer hybrid composites. In order to solve the above issue, based on the multi-scale uncertainty propagation analysis method, this paper realizes the propagation analysis and accurate measurement of the macro-parameter uncertainty through the neural network model, and defines the multi-scale uncertainty propagation law of interlayer hybrid composites. In the case of considering uncertainty of the macro material properties, multi-objective optimization algorithm is used. The co-optimized design of buckling stability of the stiffened panel and structural lightweight is carried out, resulting in maximized critical buckling load and reduced mass of the stiffened panel.