The use of organic amendments in agriculture is a common practice due to their potential to increase crop productivity and enhance soil health. Indeed, organic amendments of different origin and composition (e.g., animal slurry, manure, compost, sewage sludge, etc.) can supply valuable nutrients to the soil, as well as increase its organic matter content, with concomitant benefits for soil health. However, the application of organic amendments to agricultural soil entails a variety of risks for environmental and human health. Organic amendments often contain a range of pollutants, including heavy metals, persistent organic pollutants, potential human pathogens, and emerging pollutants. Regarding emerging pollutants, the presence of antibiotic residues, antibiotic-resistant bacteria, and antibiotic-resistance genes in agricultural amendments is currently a matter of much concern, due to the concomitant risks for human health. Similarly, currently, the introduction of microplastics to agricultural soil, via the application of organic amendments (mainly, sewage sludge), is a topic of much relevance, owing to its magnitude and potential adverse effects for environmental health. There is, currently, much interest in the development of efficient strategies to mitigate the risks associated to the application of organic amendments to agricultural soil, while benefiting from their numerous advantages.