Linear and hyperbranched polyglycerol-based mannosides and fucosyllactosides were developed as nanomolar binders of mannose binding lectin (MBL) and DC-SIGN using label free microscale thermophoresis (MST) and surface plasmon resonance (SPR) techniques, respectively. While there was a small preference for hyperbranched polyglycerols in the case of MBL inhibitors, a clear advantage of ligand presentation on linear polyglycerol scaffolds was observed for DC-SIGN.