The chromatography methods such as HPLC, HPTLC etc. were developed for simultaneous estimation of multiple fixed-dose combination products of metformin hydrochloride which need single chromatography condition to save solvent consumption. The method was developed by the implementation of analytical quality by design approach based on principles of quality risk management (QRM) and design of experiments (DoE) as per regulatory requirements. QRM was applied for the analysis of twenty potential method risk parameters using the Ishikawa diagram and quality risk assessment according to ICH Q9 guideline. DoE was applied by Taguchi OA screening design and Box-Behnken response surface analysis method. Method operable design range was navigated for optimisation of critical method risk parameters as per the analytical target profile for development of the method. The developed method was applied for the analysis of three different fixed-dose combination products of metformin hydrochloride. By the QRM process, seven method risk parameters were found critical for the development of the method. After the Taguchi screening design, the main effect of mobile phase composition, %w/v of ammonium acetate and saturation time was found to be significant. The results of the Box-Behnken design showed a quadratic relationship between CMPs and CMAs. The developed method was found to be specific, accurate and precise. The results of the assay were found in good agreement with the labelled claim. The developed method can analyse three different fixed-dose combination products of metformin hydrochloride which required three different chromatography methods. Hence, the method is versatile and eco-friendly.