A range of in vitro models of the gastro-intestinal tract have been developed that vary in their composition and complexity. Such models could be useful for assessing the hazard of ingested nanomaterials (NMs). This study aims to compare the relative sensitivity of four intestinal in vitro models (undifferentiated Caco-2 cells, differentiated Caco-2 cells, Caco-2/Raji B and Caco-2/HT29-MTX co-cultures) the natural clay montmorillonite (MMT) and man-made silicon oxide (SiO2) NMs, both of which are exploited in diverse health and consumer products that may lead to their ingestion. No significant impacts of SiO2 NMs and MMT were identified with respect to cell viability, transepithelial electrical resistance (TEER), cell morphology and reactive oxygen species (ROS) production, across all models. This suggests that SiO2 NMs and MMT were relatively low in toxicity compared to other nanomaterials which were tested previously (such as CuO) and that the models were comparable with respect to responsiveness. Further comparison of these results with in vivo data in the future would help to identify which in vitro models provide a good prediction of NM toxicity. This knowledge will help inform what testing strategies are employed when assessing the toxicity of ingested NMs in the future.