Water scarcity and drought are an increasingly frequent and widespread phenomenon in the European Union. In Southern Europe, agriculture, among other sectors, has the highest demand for abstracted water, hence it is greatly affected by the water shortage. Irrigation with treated wastewater water is a common approach used to address increasing pressure on water resources. However, there are environmental and health risks related to wastewater reuse, e.g., the occurrence of antibiotics and antibiotic resistant bacteria. In fact, antibiotic resistance has become a serious and growing threat to human health. Due to the aforementioned, a pilot-scale constructed wetland system was built as a tertiary treatment for real domestic wastewater. This simple, natural-based, and low energy-intensive system was evaluated for the removal of antibiotics (i.e., sulfamethoxazole, ofloxacin, trimethoprim, and clarithromycin) and antibiotic resistance genes. Whilst the fate of parent antibiotics has been thoroughly researched, the occurrence of their biotransformation products and their selective pressure on the bacterial resistance is less understood. In this study, special attention has been given to the identification of antibiotic biotransformation products. In addition, conventional water quality parameters were analyzed (e.g., BOD, COD, pH, conductivity, dissolved oxygen, redox potential). Phragmites australis was used as a phytoremediation plant; two operation modes, unsaturated and partially saturated, were compared. Previous research has highlighted the role of soil and endophytic microorganisms in phytoremediation of organic contaminants. Trichoderma spp., has shown to possess genes for degradation of pharmaceuticals (Manasfi et al, 2020) and to modulate uptake and metabolism of pharmaceuticals in plants (Peña-Herrera et al., in preparation) but research in this field is still scarce. Here, the effect of bioaugmentation (with Trichoderma sp.) on the overall efficiency of the system was evaluated in real operational conditions. Preliminary results showed how bioaugmentation could be used in constructed wetlands as additional, low-cost, purification technique to reduce antibiotic and/or their potential harmful transformation products and antibiotic resistance genes associated and in this way help in minimizing the generated imbalances in agriculture between the water demand and water availability.