The Driver-Pressure-State-Impact-Response (DPSIR) framework was applied in a central area of the Salento peninsula to identify environmental and human factors influencing the quality of groundwater and propose strategies for its preservation. In accordance with this approach, a set of indicators providing a simplified description of the various components of a complex environmental system, directly or indirectly related to groundwater quality, was selected to obtain information useful for the management of water resources. A total of 42 indicators were taken into account: 11 for the driving forces, 5 for pressures, 21 for states, 2 for impacts and 3 for responses. The chemical and microbiological characterisation of the deep aquifer in the territory of Grecìa Salentina highlighted a number of cases of contamination attributable to risk factors present in the area. The study enabled the formulation of (a) hypotheses regarding the causes of poor water quality, and (b) management strategies for resolving the negative aspects of the overall state of health of the aquifer.