Salinity represents a significant challenge to global agriculture and crop production, emphasizing the need for innovative strategies to enhance the salt tolerance of various crop species. Selenium (Se), an essential inorganic plant elicitor, has shown potential in mitigating salinity stress. This study investigated the effectiveness of Se in alleviating salt stress in Carthamus tinctorius L. Two weeks old seedlings were exposed to NaCl and sodium selenate. Selenium application reduced the adverse effects of salinity on physiological, molecular, and biochemical processes compared to the control. Se treatment increased the proline and protein content in safflower under saline conditions. Furthermore, Se mitigated oxidative stress by enhancing the activities of POX and PPO in both leaf and root tissues. Se promoted the biosynthesis of secondary metabolites, leading to increases in total phenolic, flavonoids, and anthocyanin content under saline conditions. SOD and PAL genes expression increased in salinized C. tinctorius and treated with Se as a molecular strategy to cope with the salinity. The findings of this study elucidated some biochemical, physiological, and molecular mechanisms. These mechanisms underlie selenium-mediated salt resilience in C. tinctorius.