Insects have been proposed as a substitute for livestock in future foods as a source of protein and micronutrients. In an attempt to compare iron bioaccessibility between different insect species to human intestinal epithelia, we discovered unexpected cytotoxic effects using standard procedures for estimating iron bioaccessibility. Pre‐confluent and confluent, differentiated epithelia of human intestinal Caco‐2 cells were exposed to simulated gastrointestinal digests of three edible insect species (meal worm, desert locust and black cricket) at varying concentrations. Cell survival and metabolic assays indicated cell death already at low levels of insect digests. Proteomic analyses revealed increased levels of cellular stress markers. Taken together, the data indicate that the investigated insects are cytotoxic to cultured human intestinal cell epithelia. Support or Funding Information This work was supported by the UK Biotechnology and Biological Sciences Research Council Nottingham‐Rothamsted Doctoral Training Partnership [grant number BB/J014508/1] and by the Swedish Research council FORMAS (grant # 2014‐417).