Supramolecular cage chemistry is of lasting interest because, as artificial blueprints of natural enzymes, the self-assembled cage structures not only provide substrate-hosting biomimetic environments but also can integrate active sites in the confined nanospaces for function synergism. Herein, we demonstrate a vertex-directed organic-clip chelation assembly strategy to construct a metal-organic cage Fe4L68+ (MOC-63) incorporating 12 imidazole proton donor-acceptor motifs and four redox-active Fe centers in an octahedral coordination nanospace. Different from regular supramolecular cages assembled with coordination metal vertices, MOC-63 comprises six ditopic organic-clip ligands as vertices and four tris-chelating Fe(N∩N)3 moieties as faces, thus improving its acid, base, and redox robustness by virtue of cage-stabilized dynamics in solution. Improved dehydrogenation catalysis of 1,2,3,4-tetrahydroquinoline derivatives is accomplished by MOC-63 owing to a supramolecular cage effect that synergizes multiple Fe centers and radical species to expedite intermediate conversion of the multistep reactions in a cage-confined nanospace. The acid-base buffering imidazole motifs play a vital role in modulating the total charge state to resist pH variation and tune the solubility among varied solvents, thereby enhancing reaction acceleration in acidic conditions and rendering a facile recycling catalytic process.