Conventional fertilization practices in agroecosystems concern the supply of bioavailable nutrients, such as mineral fertilizers. A consolidated alternative to restoring the long-term fertility of agricultural soils is their amendment with organic fertilizers. Soil amendment with biowaste compost or sewage sludge represents a sustainable strategy to avoid the landfilling of organic matter derived from urban waste and sewage sludge. This study aims at validating the use of quality biowaste compost and sewage sludge from secondary sedimentation (alone or in combination with mineral fertilizers) in a Mediterranean agroecosystem and their effects on soil chemical and biological quality, with a view to verifying the maintenance of soil fertility and functionality. In particular, the dynamics of soil organic matter, pH, potentially toxic elements and microbial community functionality were assessed, in experimental mesocosms, during 6 months of incubation. The research showed that, while soil amendment with biowaste compost induces positive effects on soil organic matter and phosphorous concentrations, as well as on microbial community functionality, the amendment with the selected sewage sludge does not determine any benefit to the microbial community or any danger in relation to soil potentially toxic element concentrations and toxicity. The quantity of sewage sludge employed, chosen according to regional directives, was thus not enough to stimulate the edaphic microflora activity.