Encapsulation of curcumin (Cur) into nanomaterials has been a promising strategy for enhancing its unfavorable properties and maximizing its health benefits. In this study, a novel Cur-loaded mesoporous polydopamine (PDA)-based nanoparticles (Cur-MPNs) further decorated with polyethylene glycol-chitosan (PC) complexes were fabricated for the first time. The results show that the MPNs-PC nanocomposite exhibits a satisfactory loading capacity and superior stability. In vitro studies revealed that nano-encapsulated Cur exhibited enhanced antioxidant activities and pH-responsive release behaviors. More importantly, the MTT assay showed reductions in viability of human MCF-7, A549, and HCT-116 cells upon exposed to Cur-loaded nanovehicles. The representative HCT-116 cell apoptosis model, employing flow cytometry and fluorescent microscopy analyses, convincingly demonstrated that the encapsulated Cur more effectively induced apoptosis. This signifies that these MPNs-PC formulations possess considerable potential as an encapsulated system for Cur with intensified biological characteristics.