The balance between excitation and inhibition in the central nervous system is fundamental for its development and optimal functioning, with defective and/or altered GABAergic signalling (through Cl-permeable GABAA receptors) found implicated in diverse neurodevelopmental and psychiatric disorders. A major role in the maintenance of the excitation and inhibition balance is played by the Na+-dependent Cl-importer NKCC1 and the Na+-independent Cl-exporter KCC2. These cation chloride co-transporters modulate the intracellular chloride concentration and they are dysregulated or mutated in a wide variety of brain conditions. In consideration of the relevant role played by these two Cl- transporters in brain physiology and pathology, investigating their expression regulation and modulation of their activity in ageing may be of great interest. Indeed, alterations in GABAergic signalling have been already described in this phase of life. In the current study, we identified an altered expression of KCC2 in the hippocampus of old mice (24-month-old) and elderly people (over 75 years old), when compared to control mice (2-month-old) and young adult people. Pharmacological targeting of KCC2 by a commercial compound rescued the age-associated cognitive impairment in long-term and short-term memory, which we observed in behavioural studies. Altogether, our studies indicate KCC2 as a possible target to rescue cognitive impairment in the elderly population.