We have successfully designed and synthesized polycarbonate-based brush polymers with detachable, disulfide-linked side chains. A polycarbonate backbone with disulfide-linked, hydroxyl-terminated pendant side chains was first prepared. Poly(trimethylene carbonate) or poly(l-lactide) brushes were then grafted from the terminal hydroxyl groups using an acid- or base-catalyzed ring-opening polymerization. Inspired by how cells use glutathione to mediated reduction of disulfides in cytoplasmic proteins, we also demonstrate that the side chains are easily detached under mild reductive conditions (e.g., with 1,4-dithiothreitol). l-Lactide and trimethylene carbonate were selected as model building blocks for the polymer grafts because of their commercial availability and routine use in polymeric drug delivery systems. © 2013 American Chemical Society.