: The aim of this study was to investigate the changes in the SIRT family, the effects of sirtuins on kidney graft function, and their potential as biomarkers in patients who develop rejection after kidney transplantation. : Blood samples were collected from 45 kidney transplant patients before and after rejection. Some of these patients experienced T-cell-mediated early rejection (TCMR), while others presented antibody-mediated late rejection (ABMR). The mRNA expression levels of SIRT-1, SIRT-3, and SIRT-7 were measured via real-time PCR, while the protein levels of SIRT-1, SIRT-2, SIRT-3, SIRT-5, and SIRT-7 were assessed using ELISA. Patients were grouped based on rejection type and histological characteristics. Statistical analyses were performed using SPSS software (V23). : The mean age of the patient group was 42.22, while the control group had a mean age of 35.23 ( = 0.002). SIRT-1, SIRT-3, and SIRT-7 levels were significantly higher in patients with rejection ( < 0.001). In patients with late-stage rejection, SIRT-3 was found to be associated with interstitial fibrosis and C4d accumulation. SIRT-7 levels showed a weak correlation with potassium levels ( = 0.014). : Our findings demonstrate significant changes in the SIRT family during both early- and late-stage rejection processes. Particularly, the role of SIRT-3 in the late stage is highlighted, suggesting the potential use of this gene as a biomarker for managing rejection processes. These findings could provide valuable insights for developing treatment strategies in organ transplantation.