AbstractInnate immunity is the immediate and exclusive defense mechanism in invertebrates. It acts against foreign agents and pathogens. In insects, this defense mechanism involves a combination of humoral and cellular responses, orchestrated by specific recognition receptors and the activation of various signaling pathways. Remarkably, Toll and Toll‐related proteins play a pivotal role in insect immunity by inducing the production of antimicrobial peptides (AMPs) in response to pathogen attacks. Toll receptors, which are type I transmembrane proteins, significantly affect insect development and the innate immune response, primarily via the nuclear factor kappa‐B signaling pathway. The Malpighian tubules of insects play a crucial role in waste elimination, hemostasis maintenance, and immune defense. The Toll signaling pathway in Malpighian tubules is mainly involved in the production of AMPs. This review provides valuable insights into the mechanisms of the Toll signaling pathway and the morphological and physiological attributes of Malpighian tubules. Moreover, it discusses the classification and functionalities of AMPs synthesized in Malpighian tubules in response to pathogens, thereby contributing to our understanding of innate immunity in insects.