The routinely employed periodic boundary conditions complicate molecular simulations of physiologically relevant asymmetric lipid membranes together with their distinct solvent environments. Therefore, separating the extracellular fluid from its cytosolic counterpart has often been performed using a costly double-bilayer setup. Here, we demonstrate that the lipid membrane and solvent asymmetry can be efficiently modeled with a single lipid bilayer by applying an inverted flat-bottom potential to ions and other solute molecules, thereby restraining them to only interact with the relevant leaflet. We carefully optimized the parameters of the suggested method so that the results obtained using the flat-bottom and double-bilayer approaches become mutually indistinguishable. Then, we apply the flat-bottom approach to lipid bilayers with various compositions and solvent environments, covering ions and cationic peptides to validate the approach in a realistic use case. We also discuss the possible limitations of the method as well as its computational efficiency and provide a step-by-step guide on how to set up such simulations in a straightforward manner.