Chronic hepatitis B virus infection is a major global health concern, accounting for substantial liver-related illness and death worldwide. The complex protein profile present in both blood serum and saliva is composed of numerous individual proteins, which collectively contribute to the overall protein composition of these bodily fluids. Valuable diagnostic insights can be gleaned from assessing alterations in total serum protein concentrations or variations within distinct protein fractions. Current study aimed to investigate the influence of hepatitis B disease on the matter of total protein concentration, as well as the levels of albumin and globulins, exploring the feasibility of utilizing saliva as a diagnostic fluid to monitor fluctuations in these parameters is of paramount importance. This line of research shows potential for replacing serum with saliva for such diagnostic purposes. This study about the individuals infected with chronic hepatitis B virus was conducted where a total of 50 patients with hepatitis B and 50 with the control group. Concentrations of serum and saliva total proteins and albumin were measured, meantime the concentration of globulin and the ratio of Albumin/Globulin were calculated in both saliva and serum samples of the patients and the healthy groups. Agarose gel electrophoresis was employed to detect the changes in the protein profile in these samples. The findings from total protein measurements indicated a slight non-significant decrease in serum samples, whereas a highly significant decrease (P=0.002) was observed in the saliva samples of patients with hepatitis B in contrast to the healthy control group. Furthermore, a significant decrease (P<0.001) in albumin concentration was noted in the serum samples of these patients, while no significant variation was observed in the saliva samples compared to the respective control groups. However, no significant differences were observed in the concentration of globulins in serum samples, nor the [albumin] /[globulin] ratio. In patients with hepatitis B, the total protein and albumin concentration were found to decrease in both serum and saliva samples. Age and gender were found not significantly affect total protein and albumin levels in the patient group. Albumin concentration decreased in patients compared to the control group when their total protein concentration ranged from 6.1 to 8.4 g/dl. Based on the results of this study, it can be concluded that chronic hepatitis B influences the composition and concentration of serum and salivary proteins