The synthesis of multivalent ligands able to selectively bind enzymes has produced a multitude of new glycomimetics anchored to different macrocyclic scaffolds. However, in this scenario, the studies focused on therapeutically relevant enzymes are still scarce. Resorcinarenes offer the opportunity to attach several bioactive functions to different positions, thereby accessing different topologies of the multivalent constructs. In this work, multimerization of the pyrrolidine iminosugar DAB-1 onto resorcinarene scaffolds has been addressed. The synthesized new architectures show a remarkable multivalent effect towards GMIIb, the recombinant Drosophila homolog of the tumor over-expressed human Golgi α-mannosidase II, over other α-mannosidases. Computational studies shed light on the origin of their multivalent effect as well as on their relative inhibitory potency.