Ionic diodes, referring to fluidic devices with ion rectifying properties, have recently received considerable attention from the nanofluidics community due to their promising applications particularly in promoting clean energy. The past ionic diodes were realized with nanometer-scale pores, but those nanofluidic devices suffer from high resistance and high fabrication cost, thus limiting their practical applications. Here we report a simple strategy to fabricate a robust mesoscale ionic diode by electrokinetic functionalization of single conical mesoscale pores (700–800 nm tip diameter) with high molecular weight poly-L-lysine. Experiments show that the mesoscale ionic diode exploited can still function in mild neutral and 10 mM salt solution, under conditions at which the pore size is over 200-fold larger than the Debye length. The findings are supported by our simulation that attributes the mesoscale rectification to the effect of ion concentration polarization induced by the coating of highly space-charged polyelectrolytes. The application of the exploited mesoscale ionic diode in osmotic energy harvesting is also demonstrated, which achieves a power up to 254 pW at “neutral” pH and a 1000-fold salinity gradient, 5 times more than that of all the state-of-the-art single nanopore-based devices reported under the same testing conditions.