Desalination with electrodialysis requires cell designs for optimal flow distribution. Such units include polymeric frames, electrodes, membranes and spacers. Frames are used for mechanical support of electrodes and hydraulic connectors. Their geometry needs to be customized for appropriate fluid management and hydraulic compartmentalization. Typically, such electrodialysis frames are manufactured by drilling solid plastic blocks. However, design flexibility is required to fit the increasing number of developments incorporating new materials and flow inter-connectivity. Here we propose additive manufacturing coupled with computational design to optimize flow dynamics and their coupling with physical devices. First, CAD models are proposed to incorporate major improvements in process lines, and to integrate internal manifold cavities. Even fluid flow and pressure drop distributions are verified by numerical models at given flowrates. The frames were 3D printed and assembled with electrodes and membranes to investigate their performance, and to experimentally confirm numerical predictions. Compared to conventional frames, and as a result of the even distribution of the fluids inside the cell, it was possible to reach an improved (21% higher) limiting current density while ensuring pH stability. Finally, our approach can be integrated in new designs, taking advantage of material selection and geometrical complexity of 3D-printing to add novel functionalities.