The　design　of　bright　NIR-II　luminescent　nanomaterials　that　enable　efficient　labelling　of　proteins　without　disturbing　their　physiological　properties　in　vivo　is　challenging.　We　developed　an　efficient　strategy　to　synthesize　bright　NIR-II　gold　nanoclusters　(Au　NCs)　protected　by　biocompatible　cyclodextrin　(CD).　Leveraging　the　ultrasmall　size　of　Au　NCs　(＜2　nm)　and　strong　macrocycle-based　host-guest　chemistry,　the　as-synthesized　CD-Au　NCs　can　readily　label　proteins/antibodies.　Moreover,　the　labelled　proteins/antibodies　enable　highly　efficient　in　vivo　tracking　during　blood　circulation,　without　disturbing　their　biodistribution　and　tumor　targeting　ability,　thus　leading　to　a　sensitive　tumor-targeted　imaging.　CD-Au　NCs　are　stable　in　the　harsh　biological　environment　and　show　good　biocompatibility　and　high　renal　clearance　efficiency.　Therefore,　the　NIR-II　biolabels　developed　in　this　study　provide　a　promising　platform　to　monitor　the　physiological　behavior　of　biomolecules　in　living　organisms.