A general understanding of redox homeostasis in An. gambiae midgut epithelial cells under different oxidative conditions during P. falciparum ookinete invasion is missing. We used an ex vivo midgut culture model to understand AgTrx-1 protein expression pattern in An. gambiae midguts under oxidative stress of the ROS inducer, tert-butyl hydroperoxide (tBHP). We then quantified the midgut proteomic expression profile to understand organ-level regulation of the response to oxidative stress. An. gambiae midguts under low (50M) and high (200M) tBHP concentrations were enriched in ribosomal proteins (RPs), consistent with cells undergoing ribosomal/nucleolar stress. Nevertheless, these midguts were also enriched in peptidases, integral membrane proteins, and cytochrome P450s indicating cells that are undergoing protein processing and folding through post-translational modification (PTMs), and detoxification of toxic compounds through active efflux. This response to oxidative stress was strikingly dissimilar to that observed from previous studies with another dipteran, Drosophila following oxidative stress induction. Our data indicates that the response to tBHP induced oxidative stress is mild and suggests that the associated antioxidant response is similar to what is observed during midgut invasion of P. falciparum okinete. Furthermore, our data shows that ribosomal/nucleolar stress is crucial in the regulation of oxidative stress in An. gambiae midguts. Given this importance, its possible to develop mechanisms to perturb this ribosomal/nucleolar stress response in An. gambiae resulting into unmanageable levels of oxidative stress exposure to Plasmodium parasite in the midgut, yet still allowing the mosquito to survive the perturbation. Unmanageable levels of oxidative stress could result to harmful effect to the Plasmodium and eventually its death resulting into halting of its transmission.