This study investigated the impact of two caustic and one acidic cleaning formulations (namely MC11, PC98, and MC3, respectively) on the properties and separation efficiency of three different nanofiltration (NF) membranes (namely NF270, NF90 and TFC-SR100). Overall, the impact of chemical cleaning on surface properties and rejection was membrane and cleaning reagent specific. It was driven mostly by conformational changes of the membrane polymeric active skin layer in response to an extreme caustic or acidic environment and to a certain extent by the adsorption of cleaning additives (e.g., surfactants and chelating reagents). The influence of chemical cleaning on the membrane properties and separation efficiency was most severe for the NF270 due to its loose and very thin active skin layer. Caustic cleaning using either the MC11 or PC98 formulations led to a significant increase in the permeability and a considerable decrease in the rejection of both inorganic salts and trace organic contaminants by the NF270 membrane. In contrast, acidic cleaning using the MC3 formulation caused a small decrease in the permeability of the NF270 membrane. The influence of chemical cleaning on the NF90 and TFC-SR100 membranes was much less significant, possibly because of their thicker and denser active skin layer. The results reported here demonstrated that the impact of chemical cleaning was not permanent and could be minimised by adapting an appropriate strategy involving caustic cleaning followed by acidic cleaning. FTIR analyses of the virgin and cleaned membranes showed no discernible impact of chemical cleaning on the bonding structure of all three membranes investigatedhere.