The abuse of toxic organic solvents and surfactants has caused immeasurable damage to human health and the environment. For this reason, for sustainable pest control, based on the concept of green chemistry, there is an urgent need to develop a new type of nano-based pesticide formulation that does not use harmful additives. Here we reported that two natural small molecules spinosad (SSD) and sulfamic acid (SA) self-assembled through noncovalent interactions to form SSD-SA nanoparticles (SSD-SA-NPs) without the involvement of organic solvents and carriers. The results showed that the optimized mass ratio between SA and SSD at pH 5 and 35 ℃ in aqueous solution for the formation of SSD-SA-NPs was 1: 4. The core-shell structure of nanospheres with a particle size of approx. 7 nm had excellent physical and chemical properties, such as strong positive charges (+47.8 mV) and good surface activity. SSD-SA-NPs showed good rapid action against Plutella xylostella larvae and Frankliniella occidentalis, and the insecticidal activities of SSD-SA-NPs were significantly higher than those of commercial SSD suspension concentrations. The genotoxicity assessment showed that the genotoxicity of SSD compared to Vicia faba was reduced by the combination of the self-organization technology and thus SSD-SA NPs had a low risk for the plant cells. These small molecular SSD-SA NPs, developed through a simple and environmentally friendly manufacturing process, have great application potential in sustainable crop protection.