This study evaluated the effects of acute exposure of Aedes aegypti third instar (L3) larvae to the saline extract of Opuntia ficus‐indica cladodes on the biological cycle and fertility of the emerging adults. For this, larvae were treated for 24 h with the extract at ¼ LC50 (lethal concentration to kill 50% of larvae), ½ LC50 or LC50; the development and reproduction of the emerged adults were evaluated after a recovery period of 9 days. The resistance of proteins in the extract to hydrolysis by L3 digestive enzymes and histomorphological alterations in the larval midgut were also investigated. The extract contained lectin, flavonoids, cinnamic derivatives, terpenes, steroids, and reducing sugars. It showed a LC50 of 3.71% for 48 h. The data indicated mean survival times similar in control and extract treatments. It was observed development delay in extract‐treated groups, with a lower number of adults than in control. However, the females that emerged laid similar number of eggs in control and treatments. Histological evaluation revealed absence of bacterial and fungal microorganisms in the food content in midguts from larvae treated with cladode extract. Electrophoresis revealed that three polypeptides in the extract resisted to hydrolysis by L3 digestive proteases for 90 min. The lectin activity was not altered even after 24‐h incubation with the enzymes. In conclusion, the extract from O. ficus‐indica can delay the development of Ae. aegypti larvae, which may be linked to induction of an axenic environment at larval midgut and permanence of lectin activity even after proteolysis.