Agricultural production of leafy vegetables in Mediterranean countries aims to achieve high yields without elevated nitrate contents in the edible parts. This implies an adjusted nutrient management, especially of nitrogen (N), in irrigated horticultural systems under semiarid conditions. These horticultural systems are highly relevant in SE Spain from an economic perspective. However, the management of N fertilizer, generally applied in large amounts (150–250 kg N ha−1 in a split application), could trigger losses of reactive N to the environment. The use of novel fertilizers may fulfill the nitrogen requirements of the crop, but should also help to decrease the environmental impacts of production, thus achieving carbon-neutral horticultural systems through (e.g.) enhancement of carbon (C) stocks and greenhouse gases (GHG) emission abatement. In this experiment, eight different fertilizing scenarios at a normalized N application rate of 150 kg N ha−1 were assessed in terms of crop yields, nutrients uptake, C stocking capacity, and yield-scaled GHG emissions. Inorganic NPK fertilizers, digestates, biosolids, composts, and vermicomposts were included among this set of fertilizers. Our results show that organic-based stabilized materials, especially composts, lowered the NO3− concentration in spinach leaves, in comparison to organic raw materials and synthetic fertilizers. They also produced yields similar to those of slow-release synthetic fertilizers, but with a significant increase in soil organic C 61 days after application. In general, N2O emissions were positively affected by the treatments. Nevertheless, direct N2O emissions were generally low (the highest emission factor, 0.13, being for the biosolid treatment) due to the combined mitigating effect of both the edapho-climatic conditions and the management practices. In general, cumulative CO2 emissions were high in all organic scenarios compared to the control treatment (299 kg C-CO2 ha−1), the highest values being observed in the treatment with biosolid (589 kg C-CO2 ha−1), probably due to differences in the labile organic C contents. In conclusion, some of the organic-based treatments showed multiple positive effects: on crop quality (i.e. leaf N content), crop yields, and GHG mitigation potential. Based on our results, the use of these materials represents an optimized N fertilizer strategy to help achieve a circular economy, by closing nutrient loops and decreasing the environmental impacts of horticultural production systems in semiarid regions of southern Europe.