End-stage renal disease (ESRD) treatment includes dialysis and kidney transplantation. Transplant rejection is a major barrier to transplant success. One of the markers mentioned in previous studies on renal function in patients with renal failure for various reasons is periostin (POSTN). The expression of POSTN correlates with interstitial fibrosis and reduced renal function. One of the limitations in this regard is the effect of oral lesions on the POSTN level. This study was conducted aimed to measure the relationship between salivary and serum POSTN and renal function in patients with a history of a kidney transplant, taking into account all the conditions affecting POSTN. In this study, serum and saliva samples were taken from 23 transplant patients with normal function (NF) and 29 transplant patients with graft failure (GF). At least one year had passed since the transplant. Before sampling, a complete oral examination was performed. Salivary and serum POSTN was examined by ELISA. The results were analyzed by SPSS software. The POSTN level in the serum of the NF group (191.00 ± 33.42) was higher than GF patients (178.71 ± 25.68), but the difference was not significant (P = 0.30). Salivary POSTN in NF patients (2.76 ± 0.35) was significantly higher than GF patients (2.44 ± 0.60) (P = 0.01). The superiority of saliva as a diagnostic fluid includes ease of collection and storage, and non-invasiveness, all of which can lead to the replacement of blood with this bio-fluid. The significant results of salivary POSTN may be due to the lack of serum disturbing factors. Saliva is an ultra-filtered fluid from serum and therefore there are fewer proteins and polysaccharides attached to biomarkers in saliva and the accuracy of measuring these biomarkers in the saliva is more valuable than serum.