Pesticides are important tools to control crop diseases and pest hazards, guaranteeing the crop harvest. Natural products and their derivatives are major sources of novel pesticides and play indispensable roles in various fields, such as insecticide, fungicide, plant growth regulation, immune regulation and so on. In recent years, numerous fields of biotechnology have made great progress, like genomics, proteomics and structural biology. And thus, the identification of pesticide targets based on natural products and the creation of novel pesticide molecules based on target structures developed rapidly. The concept, rational design, received more attention in pesticide creation. In this article, the discovery of active natural products based on existed targets or novel targets verifying by natural products were demonstrated by several cases, and the subsequent progress in the development of new pesticides were also discussed. The cases explained the important role of natural products in bridging new targets and novel pesticides.