This chapter covers the challenges of usages of deep eutectic solvents, toxicity and socioeconomic and environmental impacts. Deep eutectic solvents (DESs) are emerging green solvents that are widely used in various applications, such as organic synthesis, electrochemistry, extraction of active compounds, synthesis and separation processes, solubility enhancement of hydrophobic drugs, and drug delivery formulations. Thus, the used DES must be well characterized not only its physicochemical properties but also cytotoxicity to ensure its implementation in real industry processes competitive, safer, and eco-friendly solvents compared to conventional solvents. All users either in research and developments of industry must have regular safety assessment of handling practices and disposal methods of DES aligned with sustainable development gold and circular economy. Furthermore, the long-term environmental impact needs to be studied when DES becomes widely used, as there is a possibility of bioaccumulation and the impact of breakdown products of DES in our environment. Regulations and guidelines for DES in all applications should be established to ensure their safe use and sustainability, especially in large-scale applications.