The preparation of polyhedral oligomeric silsesquioxane (POSS) derivatives possessing different types of alkyl substituents and their application as a molecular filler for simultaneously lowering refractive indices and enhancing thermal and mechanical properties of poly(methyl methacrylate) (PMMA) are described. The modified POSS derivatives were prepared in situ through sol-gel reactions in the presence of two types of alkylsilanes. The products had molecular distributions originating from the formation of cubic and pentagonal prism structures and variable introduction ratios of alkyl substituents. Owing to the reduction of symmetry, the POSS fillers showed high miscibility with PMMA. From optical and thermal measurements, it was demonstrated that the POSS fillers with dual types of substituents can lower refractive indices (RIs) of PMMA matrices and enhance thermal and mechanical properties.