(1) Background: Electronic cigarettes are gaining more popularity not only among cigarettes smokers. Firstly, e-cigarettes were perceived as less harmful than traditional cigarettes, however, nowadays, they are arousing more controversy. The aim of this study was to assess the impact of e-cigarette usage on selected physicochemical properties of saliva. (2) Methods: The study population included 128 patients: 40 patients using e-cigarettes, 39 patients smoking traditional cigarettes, and 49 non-smoking patients (non-smokers). Laboratory tests involved verification of saliva values of pH and concentration of total protein, calcium, and phosphates. (3) Results: Among e-cigarette users, the value of pH was lower and the concentration of total protein, calcium, and phosphates was higher than in the group of non-smokers. Statistically significant differences were observed in relation to calcium. Among traditional cigarette smokers, the value of pH was lower, concentrations of total protein and phosphates were higher than in the group of non-smokers. Statistically significant differences were observed in relation to total protein. (4) Conclusions: Saliva of e-cigarette users presents changes in physicochemical composition in comparison to traditional cigarette smokers and non-smokers, however, statistically significant differences were observed only in calcium concentration. Further longitudinal studies on a larger study group should be conducted to assess the effect of observed changes in oral health.