Soil and water characteristics and biogeochemical processes can be improved by the application of an integrated technology based on circular economy: designed Technosol. The evaluation of the effectiveness of the superficial application of a designed Technosol, with andic and eutrophic properties, on the rehabilitation of sulfide tailings of a uranium mine (Fé mining area, Spain) was the aim of this study. After 20 months of the Technosol application, the tailing rehabilitation status (Rehabilitated tailing) was compared to a non-rehabilitated tailing (Tailing). To assess the rehabilitation of these systems, several properties were analyzed: chemical characteristics of the materials and their leachates, soil enzymatic activities (dehydrogenase, β-glucosidase, acid phosphatase and urease), basal respiration and several plant endpoints from direct and indirect bioassays and pot experiment using Lolium perennse L. and Trifolium pratense L. Potentially toxic concentrations of Co, Mn and Ni were identified in both available fraction and leachates, pointing out the serious environmental risk posed by the tailing. The improvement of overall physicochemical properties in the rehabilitated tailing materials (e.g., decrease of the hazardous element concentrations in leachates and available fraction, and improvement of the fertility and structure) allowed a quick plant cover with pasture species and provided a suitable habitat for active microbial community (evaluated by increasing dehydrogenase activity and basal respiration). This improvement in the rehabilitated tailing contributed to a significant decrease in the ecotoxicological risk and the spread of hazardous elements. The field application of this specific Technosol was a promising and lasting solution for rehabilitation of this type of tailings.