Various countries have reported the resistance of mosquitoes to synthetic insecticides and larvicides. Scientists take advantage of secondary metabolites from plants and develop them into natural larvicides. Kaffir lime leaves (Citrus hystrix) as a cooking spice is of concern in this study. The main aim of this study was to identify differences in midgut histopathological changes in Ae. aegypti larvae after exposure to C. hystrix leaf extract. This research is experimental research in the laboratory. There are five treatments with three replications. Then, 20 third-instar Ae. aegypti larvae were placed into each plastic container and recorded for 24 hours. Histopathological slices of the larval midgut were produced and stained with hematoxylin and eosin (HE). A light microscope was used to identify it. Data on changes in midgut larvae were analyzed using SPSS. Mortality of the larvae was shown in C. hystrix extract groups at doses of 1,500 and 3,500 ppm. Midgut changes occur in the length of the midgut lumen, the length of the epithelium, and the loss of the epithelial cell nucleus. The cell nuclei were not visible in the extract group at a dose of 3,500 ppm. The statistical test showed that there are differences in midgut histopathological changes in Ae. aegypti larvae after exposure to C. hystrix leaf extract. We need an in-depth study of the potency of the extract C. hystrix as an alternative larvicide against Ae. aegypti for the future.