The　discovery　of　novel　high-nuclearity　oxo-clusters　considerably　promotes　the　development　of　cluster　science.　We　report　a　high-nuclearity　oxo-cluster-based　compound　with　acid/alkali-resistance　and　radiation　stabilities,　namely,　(H3O)7[Cd7Sb24O24(l-tta)9(l-Htta)3(H2O)6]·29H2O　(FJSM-CA;　l-H4tta　=　l-tartaric　acid),　which　features　a　two-dimensionally　anionic　layer　based　on　the　largest　Sb-oxo-clusters　with　28-metal-ion-core　[Cd4Sb24O24].　It　is　challenging　to　efficiently　capture　Sr2+,　Ba2+　(analogue　of　226Ra),　and　[UO2]2+　ions　from　aqueous　solutions　due　to　their　high　water　solubility　and　environmental　mobility,　while　it　is　unprecedented　that　a　novel　Sb-oxo-cluster-based　framework　material　FJSM-CA　can　efficiently　remove　these　hazardous　ions　accompanied　with　intriguing　structural　transformations.　Especially,　it　shows　fast　ion-exchange　abilities　for　Sr2+,　Ba2+,　and　[UO2]2+　(reaches　equilibrium　within　2,　10,　and　20　min,　respectively)　and　high　exchange　capacity　(121.91　mg/g),　removal　rate　R　(96%),　and　distribution　coefficient　KdU　(2.46　×　104　mL/g)　for　uranium.　Moreover,　the　underlying　mechanism　is　clearly　revealed,　which　is　attributed　to　strong　electrostatic　interactions　between　exchanged　cations　and　highly　negative-charged　frameworks　and　the　strong　affinity　of　(COO)-　groups　for　these　cations.　Proton　conduction　of　the　pristine　and　Sr2+,　Ba2+,　[UO2]2+-loaded　products　was　investigated.　This　work　highlights　the　design　of　new　oxo-cluster-based　materials　for　radionuclide　remediation　and　proton　conduction　performance.　Copyright　©　2020　American　Chemical　Society.