Organisms are known to be equipped with an adaptive plasticity as the phenotype of traits in response to the imposed environmental challenges as they grow and develop. In this study, the effects of extreme changes in oxygen availability and atmospheric pressure on physiological phenotypes of Drosophila melanogaster were investigated to explore adaptation mechanisms. The changes in citrate synthase activity (CSA), lifespan, and behavioral function in different atmospheric conditions were evaluated. In the CAS test, hyperoxia significantly increased CSA; both hypoxia and hyperbaric conditions caused a significant decrease in CSA. In the survivorship test, all changed atmospheric conditions caused a significant reduction in lifespan. The lifespan reduced more after hypoxia exposure than after hyperbaria exposure. In behavioral function test, when mechanical agitation was conducted, bang-sensitive flies showed a stereotypical sequence of initial muscle spasm, paralysis, and recovery. The percentage of individuals that displayed paralysis or seizure was measured on the following day and after 2 weeks from each exposure. The majority of flies showed seizure behavior 15 days after exposure, especially after 3 h of exposure. The percentage of individuals that did not undergo paralysis or seizure and was able to move in the vial, was also tested. The number of flies that moved and raised the higher level of the vial decreased after exposure. Animal's speed decreased significantly 15 days after exposure to extreme environmental conditions. In summary, the alteration of oxygen availability and atmospheric pressure may lead to significant changes in mitochondria mass, lifespan, and behavioral function in D. melanogaster.