An objective of the present study was to prepare colon-specific microspheres of curcumin (CUR) containing ascorbic acid (AA) for improved oral bioavailability. 3 2 factorial design was used to optimise chitosan microspheres (CSMS) containing CUR and AA. Subsequently, optimised CSMS were coated with Eudragit S-100, for delivery to colon. In vitro drug release, in vivo pharmacokinetics, and organ distribution studies were performed in Albino Wistar rats. Stabilisation of CUR in alkaline pH was successfully guarded by AA to the extent 98.5-100%. Results revealed complete amorphisation/molecular dispersion of CUR. Bioavailability enhancement of CUR and 90% of MS in colon at the end of 8 h in animals, deciphered successful design of colon-specific CUR MS. It can be concluded that AA in MS shielded the degradation of CUR. The developed double coat MS could be considered as a promising colon-targeted system for CUR aiming bioavailability enhancements.