Abstract Spodoptera cosmioides Walker (Lepidoptera: Noctuidae) is a pest of soybean and cotton crops, whose control is mainly carried out using few chemical insecticides. Diamide flubendiamide is a potential insecticide to control S. cosmioides , which is effective in controlling several pests and have little effect on beneficial arthropods and natural enemies of the pests. This study evaluated the toxicity and histopathological changes caused by flubendiamide in the midgut of S. cosmioides caterpillars. Flubendiamide is toxic to S. cosmioides (LC 50 = 23.44 mg L − 1 and LC 90 = 320 mg L − 1 ), whose survival rate after 72 h decreased from 80.92% in the control to 39.76% with LC 50, and 21.53% with LC 90 . Flubendiamide causes damage to the midgut, including epithelial disorganization, brush border degeneration, cytoplasm vacuolization, nuclear chromatin condensation and cell fragmentation, which indicates cell death and compromises digestibility. Thus, flubendiamide has the potential to control S. cosmioides caterpillars.