Analytical Quality by Design is using the Quality by Design philosophy to design analytical methods. This study focuses on the AQbD principle of creating and validating a spectrophotometric method for detecting α, β-arteether in accordance with ICH Q8 (R2) standards for the first time. The Ishikawa diagram included sample preparation, sample pH, and wavelength to get important parameters. The ratio of ethanolic PBS 6.8 to HCl was considered as a variable. While this was going on, the drug molecule's absorbance was found to be an important factor that was looked at more closely utilizing a simple mixture design of experiments method to improve method robustness and optimization. Using the Quality by Design philosophy, the new, long-lasting, precise, and accurate UV-spectrophotometric method α, β-arteether was created. The maximum absorption of α, β-arteether was reached by heating at 50°C for 30 minutes while changing the HCl concentration (for acid degradation) and ethanolic PBS 6.8. For the concentration range of 2–20 μg/mL at λmax 254 nm, the % RSD was less than 2 and R2 was more than 0.99. The LOD and LOQ of the approach that was developed were both within acceptable ranges. The proposed method could be employed in industrial settings as a swift, precise, reliable, and economical quality control technique for the frequent and concurrent estimation of α and β-arteether.