Abstract If opportunely developed and optimized, aqueous dye-sensitized solar cells can be considered a truly low impact photovoltaic device, with no toxic components. Here we report the use of design of experiments as a useful chemometric technique for the concurrent investigation of a series of experimental factors that directly influence the proper operation of these photoelectrochemical cells. Results obtained enlighten that a solid mathematical-statistical approach is fundamental to support the researchers and effectively drive the experiments towards the achievements of optimal operating conditions of any new energy device, thus bypassing the energy/time consuming steps of traditional monovariate one-factor-at-a-time method.