The daily use of synthetic detergents at a global scale is responsible for substantial environmental impacts but managerial and policy strategies to address them are largely inadequate. More sustainable and eco-friendly detergents are an appealing solution to reduce environmental impacts. Here, we developed a detergent based on cellulose nanospheres (CNSs) from agricultural waste corncob, an overlooked abundant and cheap natural source that is often discarded. Compared with conventional surfactants, CNSs stabilize at oil–water interfaces and form Pickering emulsions with enhanced stability and antiredeposition properties. CNSs show higher cleaning efficiency in removing stains from various surfaces compared with powder and liquid commercial detergents. In contrast to high toxicity of commercial detergents, CNSs are non-toxic to several mammalian cell lines, zebrafish and hydroponic lettuce. Overall, our results demonstrated the feasibility of using agriculturally derived waste CNSs as a safer, more cost-effective and sustainable alternative to commercial synthetic detergents.