This contribution explores different strategies for the synthesis of side chain functional polydepsipeptides. First, the ring-opening polymerization of side chain functional morpholine-2,5-diones is revisited and the optimized reaction conditions used for the polymerization of (Z)-L-Lys, (Boc)-L-Lys and L-allylglycine based morpholine-2,5-diones. As a first approach towards side chain functional polydepsipeptides, the deprotection of poly(Glc-alt-(Z)-L-Lys) and poly(Glc-alt-(Boc)-L-Lys) is evaluated. Although under appropriate conditions, the side chain protecting groups can be quantitatively removed, the reaction conditions used here were found to lead to backbone degradation. As an alternative approach, the thiol-ene post-polymerization modification of poly(Glc-alt-allylglycine) is explored. Free radical addition of various omega-functional thiols was found to proceed without backbone degradation and in several cases with quantitative allyl group conversion. The post-polymerization modification strategy is attractive as it obviates the need for protecting group chemistry and facilitates the synthesis of diverse libraries of side chain functional polydepsipeptides.