Metal-organic framework (MOF) nanoparticles are successfully confined in the hollow mesoporous carbon spheres (HMCSs) through space-confined synthesis methods. The prepared ZIF-67@HMCSs nanocomposites act as effective sacrificial templates, which can afford Co²⁺ sources. After a facile solvothermal reaction and sequential cation etching, yolk–shell-structured layered double hydroxide@HMCSs (LDH@HMCSs) have been synthesized. The LDH@HMCSs nanocomposite possesses a three-dimensional (3D) hollow nanocage superstructure that effectively blocks the self-stacking of LDH nanosheets and promotes ion transport. Compared to CoFe-LDH@HMCSs, and Co-LDH@HMCSs, CoNi-LDH@HMCSs exhibit superior electrochemical performance and desalination performance due to the remarkable synergistic effect between the CoNi-LDH nanosheets and mesoporous N-doped carbon shells. The resultant CoNi-LDH@HMCSs-0.4-based capacitive deionization (CDI) device exhibits excellent salt adsorption capacity (SAC, 36.41 mg·g^–1) and good cycle stability. This work will confirm the significance of constructing superstructure and open new avenues for the practical application of CDI technology in water treatment.