Water-soluble metallo-supramolecular cages with well-defined nanosized cavities have a wide range of functions and applications. Herein, we design and synthesize two series of metallo-supramolecular octahedral cages based on the selfassembly of two congeneric truxene-derived tripyridyl ligands modified with two polyethylene glycol (PEG) chains, i.e., monodispersed tetraethylene glycol (TEG) and polydispersed PEG-1000, with four divalent transition metals (i.e., Pd, Cu, Ni, and Zn). The resulting monodispersed cages C1−C4 are fully characterized by electrospray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance (NMR) spectroscopy, and single-crystal X-ray diffraction. The polydispersed cages C5−C8 display good water solubilities and can act as nanoreactors to mediate visible-light-promoted C(sp 3 )−C(sp 2 ) crossdehydrogenative coupling reactions in an aqueous phase. In particular, the most robust Pd(II)-linked water-soluble polydispersed nanoreactor C5 is characterized by ESI-MS and capable of mediating the reactions with the highest efficiencies. Detailed host−guest binding studies in conjunction with control studies suggest that these cages could encapsulate the substrates simultaneously inside its hydrophobic cavity while interacting with the photosensitizer (i.e., eosin Y).