Molecular similarity index describes the similarity between two molecules quantitatively. But acquiring the global optimal index is a complicated problem confusing the scientists. No matter what kinds of methods are used to search the best superposition of two molecules like grid-based integral or efficient iterative technique, selecting the relative situations of molecules is needed. Because of the limitations about the random search, which has always been used, it is required to test a great lot of relative situations. In this paper, an experimental method of uniform design is applied to deploy regularly the initial relative situations of molecules in 3D space, which makes the relative situations of molecules representative and even. It ensures to get global optimization within few certain numbers of initial relative situations of molecules. Parallel implementation for deploying these situations on Np processors reduces largely the running time, which can give the same final computational result as serial program. “Uniform design” combined with parallel computation searches the best superposition between two molecules rapidly with high possibilities.