The present work is conducted to develop the innovative micro sized solid oral dosage forms of Arteether using a Quality by Design technique to increase the solubility and bioavailability. The quantity of oil and the co-surfactant-surfactant ratio was employed as parameters in DoE for drug-loaded SMEDDS optimization. The particle size and zeta potential of these formulations were found to be 120 nm and −19.8 mV respectively. The studies show that 68 ± 0.2% of the drug is entrapped in SMEDDS. The solubility and in vitro dissolution performance of both drugs in self-nano emulsifying drug delivery system formulations was improved significantly as compared to pure drugs and marketed products and the in vivo studies confirmed it. A nearly 8.25-fold increase in permeability compared to AE in its pure form was observed with SMEDDS. In addition, to increase patient compliance, the liquisolid compaction technique was utilized to convert the best batch of liquid SMEDDS into solid SMEDDS, which were then encapsulated in enteric-coated capsule shells. In vivo studies in rabbits revealed that there was an increase in 8.5247% absolute bioavailability of self-nano emulsifying drug delivery system formulations compared to pure drugs with the area under the curve of Arteether from formulation was 691.2823 ± 024.13 in comparison to that of pure Arteether 79.8 ± 16.27. The Cmax was enhanced for artemether from 2.361879 ± 1.12 to 135.3684 ± 10.28. The developed formulation strategy would be potential alternative approach to enhance the bioavailability of Arteether.