We introduce a set of multicoordinating imidazole- and zwitterion-based ligands suited for surface functionalization of quantum dots (QDs). The polymeric ligands are built using a one-step nucleophilic addition reaction between poly(isobutylene-alt-maleic anhydride) and distinct amine-containing functionalities. This has allowed us to introduce several imidazole anchoring groups along the polymer chain for tight coordination to the QD surface and a controllable number of zwitterion moieties for water solubilization. It has also permitted the introduction of reactive and biomolecular groups for further conjugation and targeting. The QDs capped with these new ligands exhibit excellent long-term colloidal stability over a broad range of pH, toward excess electrolyte, in cell-growth media, and in the presence of natural reducing agents such as glutathione. These QDs are also resistant to the oxidizing agent H2O2. More importantly, by the use of zwitterion moieties as the hydrophilic block, this polymer design provides QDs with a thin coating and compact overall dimensions. These QDs are easily self-assembled with full size proteins expressed with a polyhistidine tag via metal histidine coordination. Additionally, the incorporation of amine groups allows covalent coupling of the QDs to the neurotransmitter dopamine. This yields redox-active QD platforms that can be used to track pH changes and detect Fe ions and cysteine through charge-transfer interactions. Finally, we found that QDs cap-exchanged with folic acid-functionalized ligands could effectively target cancer cells, where folate-receptor-mediated endocytosis of QDs into living cells was time- and concentration-dependent.