Fisher information is a powerful mathematical tool suitable for quantification of data `informativity' and optimization of the experimental setup and measurement conditions. Here, it is applied to X-ray diffraction and an informational approach to choosing the optimal measurement configuration is proposed. The core idea is maximization of the information which can be extracted from the measured data set by the selected analysis technique, over the sets of accessible reflections and measurement geometries. The developed approach is applied to high-resolution X-ray diffraction measurements and microstructure analysis of multilayer samples, and its efficiency and consistency are demonstrated with the results of more straightforward Monte Carlo simulations.