Background: End-Stage Renal Disease (ESRD) is a severe nephrological condition that can lead to permanent kidney damage. Therefore, early disease diagnosis is key to preventing casualties. The gold standard method of diagnosis tends to evaluate changes in sodium, potassium, calcium, phosphorus, urea, creatinine, and parathormone hormones in blood after dialysis. However, serum evaluation is not always possible or easy for patients. Therefore, saliva evaluation has been proposed in recent years as an alternative. Objectives: The current article aims to evaluate metabolite in the saliva of ESRD patients. Methods: In this descriptive-analytical study, 29 ESRD patients undergoing hemodialysis treatment were selected. Their saliva and serum samples were taken. The number of biochemical factors, including sodium, potassium, calcium, phosphorus, urea, creatinine, and parathormone hormone, was measured with an autoanalyzer device and related kits. Finally, the correlation of parameters in serum and saliva was examined using the Pearson test. Results: The results showed a significant positive relationship between the levels of sodium, urea, and creatinine in serum and saliva samples (P < 0.05). On the other hand, there was no significant relationship between the serum and saliva levels of potassium, calcium, phosphorus, and PTH (P > 0.05). Conclusions: Due to the significant correlation between some prominent biochemical factors in saliva and serum after hemodialysis in ESRD patients, saliva could be considered a non-invasive diagnostic fluid for monitoring kidney disease in the future.