The current study was aimed at preparing the curcumin nanosuspension (CUR-NS) to improve the solubility and oral absorption of CUR. Prepared from a tandem of ultra-turrax homogenization and high pressure homogenization, the CUR-NS showed spherical shape under transmission electron microscopy with an average diameter of 210.2 nm. The absorption of CUR-NS in the gastrointestinal (GI) tract was studied in rats using an in situ single pass perfusion method. It was found that the absorption percentage in stomach was 9.20% within 2 h. The absorption process in intestine was first-process with passive diffusion mechanism, and the main absorptive segments were proven to be in the duodenum and jejunum. A pharmacokinetic study was conducted in mice after oral administration of CUR at 250 mg/kg in the form of either CUR-NS or CUR suspension. The plasma concentration-time curves were both fitted to a one-compartment model and the relative bioavailability of CUR-NS to CUR suspension was 680.03%. The effects of CUR-NS on the structural properties of the intestinal mucosal membrane of rats were investigated by fluorescence polarization and circular dichroism in vitro. After treatment with CUR-NS, not only the fluidity of intestinal mucosal membrane increased but also the conformation of the membrane protein loosed, which increased the gastrointestinal absorption of CUR-NS. These studies provided the evidence that NS was valuable as an oral delivery carrier to enhance the absorption of CUR.