To achieve the effective loading and delivery of curcumin, novel disulfide-crosslinked nanoparticles based on modified dextrin were developed for the encapsulation of curcumin. Thiolated dextrin (Dt-SH) was obtained via sodium periodate oxidation and cysteamine grafting. The Dt-SH demonstrated enhanced enzyme resistance, exhibited a rough flake-like morphology, and was classified as an amorphous material. Subsequently, spherical nanoparticles with sizes ranging from 92.52 to 157.12 nm and zeta potentials between +23.59 and + 29.90 mV were self-assembled in an aqueous solution. Thiol modification promoted interconnection and aggregation of the nanoparticles. These nanoparticles exhibited pH-dependent size variations. Taking curcumin as a hydrophobic model, nanoparticles showed intestinal targeted release in vitro. Fluorescence spectroscopy and thermodynamic analysis indicated that curcumin bound to Dt-SH nanoparticles primarily through hydrogen bonding and van der Waals forces, with hydrophobic interactions contributing. These findings supported the potential of thiolated dextrin nanoparticles in the effective delivery of hydrophobic compounds.