The method was successfully developed and optimized through DOE, and data were analyzed using Design Expert® version 9.0.3.1 software. The significant effect of independent factors was analyzed using ANOVA, and the effect was also reported in the form of perturbation plots. The design of experiments provides efficient tools for the optimization of variable factors for HPLC method development. Further the method was validated and as per the results, the present method is novel, simple, accurate, precise, economic and robust for the analysis of valsartan in nanoformulations.