Salinity stress severely impacts wheat productivity, necessitating effective strategies to enhance crop resilience. This study investigates the potential of Penicillium chrysogenum CM022 as a biological agent to alleviate the impact of salinity stress on wheat (Triticum aestivum L.). P. chrysogenum CM022 improved germination of wheat seeds, particularly under salinity of 150 mM NaCl. Fungal inoculation significantly improved plant growth in terms of root length, plant height, and seedling biomass, even under high salinity conditions. Notably, inoculated plants preserved photosynthetic pigments and reduced oxidative damage, evidenced by lower levels of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA), compared to non-inoculated controls. The inoculated plants also exhibited enhanced proline and soluble sugar contents, which are crucial for osmotic adjustment under stress. Additionally, P. chrysogenum CM022 significantly increased the antioxidant capacity of wheat, boosting total phenolic and flavonoid contents, and enhancing antioxidant enzyme activity under high salinity. These findings underscore the potential of P. chrysogenum CM022 in improving wheat tolerance to salinity stress through physiological, biochemical, and antioxidant defense mechanisms, supporting its use in sustainable agricultural practices to mitigate the adverse effects of salinity on crop production.