[Sc]Sc, [Ga]Ga, and [In]In are the three most attractive trivalent smaller radiometalnuclides, offering a wide range of distinct properties (emission energies and types) in the toolbox of nuclear medicine. In this study, all three of the metal ions are successfully chelated using a new oxine-based hexadentate ligand, Hglyox, which forms thermodynamically stable neutral complexes with exceptionally high pM values [pIn (34) > pSc (26) > pGa (24.9)]. X-ray diffraction single crystal structures with stable isotopes revealed that the ligand is highly preorganized and has a perfect fit to size cavity to form [Sc(glyox)(HO)] and [In(glyox)(HO)] complexes. Quantitative radiolabeling with gallium-68 (RCY > 95%, [L] = 10 M) and indium-111 (RCY > 99%, [L] = 10 M) was achieved under ambient conditions (RT, pH 7, and 15 min) with very high apparent molar activities of 750 MBq/μmol and 650 MBq/nmol, respectively. Preliminary quantitative radiolabeling of [Sc]ScCl (RCY > 99%, [L] = 10 M) was fast at room temperature (pH 7 and 10 min). experiments revealed exceptional stability of both [Ga]Ga(glyox) and [In]In(glyox) complexes against human serum (transchelation <2%) and its suitability for biological applications. Additionally, on chelation with metal ions, Hglyox exhibits enhanced fluorescence, which was employed to determine the stability constants for Sc(glyox) in addition to the in-batch UV-vis spectrophotometric titrations; as a proof-of-concept these complexes were used to obtain fluorescence images of live HeLa cells using Sc(glyox) and Ga(glyox), confirming the viability of the cells. These initial investigations suggest Hglyox to be a valuable chelator for radiometal-based diagnosis (nuclear and optical imaging) and therapy.