The present invention includes compositions and methods of making hydrophilic nanostructured antibiotics (i.e. nanoantibiotics), including nanoantibiotics that use environmentally degradable biomolecules as the backbone building blocks, wherein the backbone building blocks can include spherical backbones such as sucroses, cyclodextrins, glycogens, and phytoglycogen with different diameters, or rod-like backbone building blocks such as dextrins, amyloses, and celluloses with different lengths. These hydrophilic nanoantibiotics with well-defined sizes and shapes can selectively disrupt bacterial membranes (i.e., serve as membrane-active antimicrobials) while being benign to mammalian cells. Depending on the size and shape difference of the hydrophilic nanoantibiotics, they can also selectively kill one type of bacteria (e.g., gram-negative) over another type (e.g., gram-positive). The environmentally degradable nanoantibiotics will have built-in dismantling “switches” to dismantle and become antimicrobial inactive in responsive to environmental stimuli once released into natural habitat, hence greatly reducing the possibility of developing bacteria resistance.
