Cellular senescence is a key driver of heart disease, yet its regulation in cardiomyocytes remains poorly understood. Selenoprotein T (SELENOT) plays a crucial role in cardiomyocyte differentiation and protection, but its role in cardiomyocyte senescence remains unknown. Here, we explore the novel role of SELENOT in preserving cardiomyocyte viability and genomic integrity during doxorubicin-induced senescence. Senescent differentiated cardiomyocytes exhibit hallmarks of cellular senescence, including increased β-galactosidase activity and elevated p53 and p21 levels, and upregulation of senescence-associated secretory phenotype (SASP) markers (i.e. MMP3, IL6, and TNFα). Additionally, senescent cells displayed disrupted cytosolic and mitochondrial redox homeostasis, which were mitigated by PSELT (a small peptide that mimics SELENOT activity). Notably, PSELT positively influenced DNA damage markers (p-γH2AX and lamin B1) and prevented ER stress regulating BIP, calnexin, IRE1α, and ERO1α expression. Intriguingly, SELENOT expression was upregulated in response to senescence, suggesting a stress-sensing redoxin function. Loss-of-function studies revealed that SELENOT deficiency led to cardiomyocyte death and DNA damage, which were only partially rescued by PSELT, supporting the existence of cross-regulatory mechanisms within the SELENOT/PSELT axis. Mechanistically, similar to SSO, an irreversible inhibitor of CD36, PSELT mitigated the senescence-induced upregulation of CD36, a key player in cardiac aging. Co-immunoprecipitation analysis demonstrated that SELENOT interacts with CD36 in both normal and senescent human cardiomyocytes. Overall, these findings underscore the essential role of SELENOT in preserving the viability and genomic integrity of senescent human cardiomyocytes and suggest that PSELT-mediated inhibition of CD36 may represent a promising therapeutic strategy for treating age-related cardiac dysfunction.