The growing demand for sustainable food production systems requires the development of innovative approaches to optimize the utilization of natural resources and reduce the environmental impact of human activities. Marine aquaculture, a significant source of marine-derived products, produces effluents rich in organic and inorganic compounds. If not properly managed, these effluents can lead to the eutrophication of aquatic ecosystems. The genus Salicornia (Salicornia spp.) has a great economic potential due to its multiple applications, ranging from culinary uses to biomass production for biofuels. Due to their natural ability to tolerate high salinity and phytodepuration capability, Salicornia species are the perfect candidates for sustainable closed-loop systems, such as aquaculture. However, the selection of wild local accessions and the optimization of cultivation practices are still poorly understood, especially in hydroponic systems using effluent from marine aquaculture. The aim of this study was to assess the adaptability of a local glasswort (Salicornia perennans Willd. subsp. perennans) to hydroponic cultivation using aquaculture effluent and to evaluate the yield and quality characteristics of the final product. Two wild accessions of S. perennans were used in this experiment. Seeds were collected from the two main saltmarshes within the Regional Park of Migliarino, San Rossore and Massaciuccoli (Pisa, Tuscany). The plants were grown for three months, in late spring, in a floating hydroponic raft system with four different nutrient solutions: a standard nutrient solution (0g/L of NaCl) for leaf vegetables; a salinized standard nutrient solution (25 g/L of NaCl); and two salinized artificial effluents (25 g/L of synthetic sea salt), one with the same mineral content of a real sea bream aquaculture effluent and the other with the same mineral content of the standard solution. In both accessions, an optimal mineral content and the addition of salt in the nutrient solution were essential for high total fresh biomass production, while the total dry mass content was not significantly influenced by the treatments. Regarding nutraceutical parameters, in both experiments, antioxidant capacity, flavonoids, phenols and nitrates showed a similar trend, with their content decreasing in salinized nutrient solutions compared to the non-salinized treatment. However, a higher total chlorophylls content was recorded in the fresh shoots grown in the non-salinized standard solution, but only for the Galanchio accession. The results show the feasibility of cultivating wild accessions of S. perennans using effluent from saline aquaculture systems. Furthermore, the mineral composition of the effluent is crucial to a high-quality product.