<p>Soil salinization poses a significant threat to potato crops, particularly in arid and semi-arid regions. This study investigated the effects of foliar application of cerium oxide nanoparticles (CeO₂-NPs) at concentrations of 0, 10, 20, and 40&#xa0;mg L⁻¹ on the growth, biochemical, and physiological responses of potato plants under both non-saline and saline conditions. Saline treatments included control, moderate salt stress (MSS) = 75&#xa0;mM and severe salt stress (SSS) = 150&#xa0;mM NaCl salinity. The results demonstrated that both MSS and SSS substantially affected the plant performance. However, application of CeO₂-NPs at the 40&#xa0;mg L⁻¹ significantly enhanced growth, biomass, physiology, and photosynthetic traits of potato plants. The severity of saline stress was associated with increased generation of reactive oxygen species (ROS). However, treatment with 40&#xa0;mg L⁻¹of CeO₂-NPs resulted in marked increase in soluble sugars (47.35%), and soluble protein (23.34%), alongside significant reduction in proline accumulation (22.13%), H₂O₂ contents (14.67%), O₂⁻ contents (32.12%), MDA contents (33.38%), and Na⁺ ions concentration (35.95%) relative to non-stressed control. Furthermore, this optimal NPs treatment enhanced the activity of key enzymes including sucrose enzyme activity (27.79%), glutamine synthetase (82.10%), sucrose phosphate synthase (33.26%), sucrose synthase activity (51.33%), nitrate reductase activity (48.20%), and starch branching enzyme (49.35%) as compared to control (0&#xa0;mg L⁻¹). Principal component analysis (PCA) and heatmap analysis revealed significant interrelationships among measured traits, underscoring their collective role in determining the crop capacity to sustain growth under salt stress. In conclusion, foliar application of CeO₂-NPs at an optimal concentration holds an effective approach for improving the salinity tolerance in potato plants.</p>