High-strength macroporous monoliths can be obtained by the simple mixing of boehmite nanofiber aqueous acetate dispersions with methyltrimethoxysilane. On the boehmite nanofiber–polymethylsilsesquioxane monoliths, we can fabricate structures smaller than a millimeter in size by computer numerical control (CNC) milling, resulting in a machined surface that is superhydrophobic and biocompatible. Using this strategy, we fabricated a superhydrophobic multiwell plate that holds water droplets to produce 3D cell culture environments for various cell types. We expect these superhydrophobic monoliths to have future applications in 3D tissue construction.