Significance The known role of the sugar d -mannose (Man) as a postal code in intracellular cargo routing has herein inspired the design of Man-presenting synthetic glycolipid-like mimics termed Janus glycodendrimers (GDs). Simple injection of a solution of Janus GDs prepared into a water-miscible solvent into buffer produces, via self-assembly, monodisperse multilamellar onion-like glycodendrimersomes (GDSs). Janus GD structural design impacts the resulting GDS architecture including surface display of Man. The latter is shown to tune reactivity to a lectin. Thus GDSs provide a model system to enable systematic studies of physiologically relevant glycan/lectin pairing.