This study investigated how the lipid composition of nanostructured lipid carriers (NLCs) affects the chemical stability and intestinal absorption of encapsulated curcumin. Spherical NLCs ranging from 210 to 260 nm in diameter were prepared, and structural transition occurred at 25.67 % (w/w) medium-chain triglyceride (MCT) content. NLCs with 30 % MCT exhibited the longest curcumin half-lives: 247.10, 50.01, and 28.30 days at 4 °C, 25 °C, and 50 °C, respectively. The optimal solid shell thickness for curcumin stabilization was 38.52 nm. Inflamed enterocytes internalized NLCs via cluster differentiation-44-mediated endocytosis due to the hyaluronic acid-receptor specific binding. The high lipid phase-interface fusogenicity and surface hydrophobicity promote the cellular uptake of NLCs containing 20 % or 30 % MCT and the caveolin-related routes. These NLCs were integrated into chylomicron assembly process and exocytosed as chylomicron mimics. Consequently, encapsulated curcumin bypassed lysosomal degradation and hepatic first-pass effect, leading to enhanced anti-inflammatory activity and bioavailability, up to 10.74 times higher.