<p>Soil salinization and heavy metal contamination, particularly their co-occurrence, pose significant challenges to agroecosystems and global food security. Exopolysaccharides (EPS) have recently emerged as promising biostimulants for mitigating heavy metal toxicity in crops. However, their potential to alleviate the combined stresses of salinity (SS) and nickel (Ni) in wheat remains poorly understood. A controlled experiment was carried out to assess the effects of SS and Ni stress, both individually and in combination, on wheat seedlings with and without EPS treatment. Growth, physiological and biochemical parameters were measured to assess stress responses and EPS-mediated mitigation. Stress conditions significantly reduced shoot and root lengths (by up to 43% and 40%, respectively), biomass accumulation (by up to 60%), and relative water content (up to 75%). The levels of oxidative stress markers (H₂O₂ and MDA) increased by more than 200%, whereas the levels of photosynthetic pigments, including chlorophyll a and b, decreased by more than 60%. EPS application mitigated these adverse effects by increasing growth, biomass, and pigment content by more than 30% and reducing oxidative stress markers by 50%. It also optimized antioxidant enzyme activities and secondary metabolite production, thereby minimizing stress-induced damage. Multivariate analyses confirmed strong positive correlations among EPS applications, growth, and physiological traits. These findings highlight EPS as a promising biotechnological solution for alleviating salinity and heavy metal stress, promoting sustainable agriculture, improving crop productivity, and reducing dependence on chemical inputs in stress-prone areas.</p> Graphical Abstract <p></p>