Compartmentalized delivery systems can achieve simultaneous encapsulation of multiple guest cargos in independent spaces and are becoming a topic of tremendous interest in medical and food disciplines. Herein, we reported a top-down assisted bottom-up approach to fabricate stable multi-chamber colloid (MCC) particles by using ferritin nanocages, which can be applied for compartmentalized loading of incompatible guest cargos. Our results demonstrated that the size of MCC particles can be regulated by controlling synthetic parameters. The primary amines of arginine and lysine residues distributed over the exterior surface and subunit-subunit interfaces of ferritin are responsible for the formation of covalent crosslinking bridges, thus, stabilizing the compartmentalized structure of MCC particles with pH value even lower to ∼2.0. Remarkably, by choosing Nile-red and FITC as guest cargos, LSCM images clearly demonstrated that Nile-red and FITC are compartmentalized encapsulated within each MCC particle, illustrating the compartmentalized loading capacity of MCC particles. Moreover, the MCC structures feature highly sealed independent compartments. When two incompatible guest cargos, chlorogenic acid (ChA) and iron core nanoparticles, are compartmentalized loaded within MCC particles, the protein shell barrier can efficiently hinder their physical contact and inhabit the redox reaction. Conversely, upon structural destruction, ChA and iron core nanoparticles are co-released and the redox reaction can be triggered, ultimately leading to the controlled release of ferrous ions for iron supplementation. This study provided a facile strategy for the construction of stable compartmentalized delivery systems, which have great potential for co-delivery of incompatible molecules in food and medical disciplines.