Treated wastewater (TWW) is considered as an alternative for agricultural irrigation. The aim of this study was to understand the medium- and long-term effects of TWW on soil physicochemical parameters. Two perimeters (P1 and P2)receiving TWW for 38 and 20 years, respectively, in Tunisiawere selected for study. In each perimeter, two water types were adopted: TWW and groundwater (GW). Soil physicochemical traits (pH, EC, and concentrations of Na+, K+, Ca2+, and Mg2+) were measured up to 100 cm, and three indexes were calculated: sodium adsorption ratio (SAR), cation ratio of structural stability (CROSS), and cation exchange capacity (CEC). Overall, all soil parameters were significantly affected in the irrigation area using GW. However, in the case of TWW, only the pH was found to be affected, increasing by 4.7% from P1 to P2. Moreover, compared to GW, TWW enhanced the soil salinity by 127%, particularly at deeper subsoils. More interestingly, the results revealed an accumulation of Mg2+, Ca2+, and K+ and a depletion of Na+ at the soil surface. Notably, TWW showed the lowest CROSS and SAR indexes, indicating the benefits of applying TWW even after long-term use in improving soil physicochemical parameters such as sodicity and structural stability. Our results provide valuable information for decision-makers to use wastewater in irrigated marginal soils.