Curcumin and Artemisinin are a poorly water-soluble drugs and its poor oral bioavailability is very low. A new self-micro emulsifying drug delivery system (SMEDDS) has been magnificently developed to improve the solubility of curcumin and Artemisinin. Appropriate compositions of SMEDDS formulation were selected via solubility studies of curcumin and Artemisinin. The formulation of SMEDDS was optimized by D-Optimal Mixture design. The optimal formulation of SMEDDS was comprised of 3ml surfactant (Tween 80), 1 ml of co-surfactant (PEG 400) and 1 ml oil (Oleic acid). The solubility of curcumin (4.4 mg/3ml) and Artemisinin (73.4 mg/3ml) was increased considerably in SMEDDS. The average particle size of SMEDDS-containing curcumin and Artemisinin was 150.7 nm. The diffusion study (in vitro) showed that more than 63.81% of curcumin and 54.91% of Artemisinin in SMEDDS could be dissolved in medium with pH 1.2 in 1 hr 30 min. Our study illustrated that the developed SMEDDS formulation held great potential as a possible alternative to traditional oral formulations of curcumin and artemisinin