Background: Waterpipe can be defined as an instrument which consumes tobacco and other substances such as honey, molasses and flavoring agents in which the smoke is filtered and cooled by passing through water. The water pipe has many toxins such as chromium, volatile aldehyde, poly hydrocarbon, lead, formaldehyde, carbon mono oxide, nicotine, arsenic and nitric acid. Aims: This study was carried out to investigate the association of some salivary constituents in relation to dental caries among water-pipe smokers. Materials and methods: Total 40 coffee-shop workers were included in this study, half of them were water-pipe smokers and the other were not smokers (passive smokers), their age was 22-23 years and 20 control without a history of water-pipe nor cigarette smoking their ages were matched with the study group were included in this study. Salivary samples were chemically analyzed for the detection of alpha-amylase, immunoglobulin A (IgA) and immunoglobulin G (IgG). Results: The total mean value of dental caries were recorded to be the highest among positive water-pipe smokers group followed by passive waterpipe smokers then control with a statistically highly significant difference (p<0.001). Regarding immunoglobulin G (IgG), the control group showed the highest value while the positive water-pipe smokers group exhibited the lower one with highly significant differences between groups p=0.000. Regarding salivary α-amylase, there is no significant difference between groups (p>0.05). The same result was seen for salivary immunoglobulin A (IgA). Conclusions: This study concluded that there is an obvious difference in the prevalence of dental caries among water-pipe smokers and control. As compared to control there is a decrease of IgG in both positive and passive water-pipe smokers.