Climate change represents a direct threat to global food security, which includes prolonged droughts caused by global warming adversely affecting agricultural crop development and yield. Symbiotic associations between plants and extremophilic microorganisms have been shown to play a crucial role in enhancing plant adaptation to environmental stress. In this study, ‘Legacy’ blueberry plants were inoculated with two endophytic fungi, Penicillium chrysogenum and Penicillium brevicompactum, isolated from Antarctic plants, to evaluate their effects on fruit productions and plant responses, to water stress. The assays were conducted under drought conditions to simulate climate change, assessing the physiological and biochemical responses of fruits from inoculated and non-inoculated plants. Results indicated that inoculated plants exhibited an improvement in the physiological responses of plants under drought stress. The inoculated plants (W-E + ) consistently perform better than non-inoculated plants (W-E-) under water stress, particularly in water potential, PSII efficiency, and photosynthetic function. Meanwhile, the fruits obtained from these plants did not show differences in fruit size, while the weight, SSC/TA and firmness were greater in the inoculated fruits compared to the non-inoculated plants under drought stress. Additionally, the fruits showed a reduction in total phenolic and flavonoid content during stress periods, while enzymatic activities of superoxide dismutase and peroxidase were enhanced under the same conditions. These findings suggest that functional symbiosis with Antarctic microorganisms may alleviate drought-induced stress in plants by modulating their biochemical activities compared to non-inoculated counterparts.