ObjectivesThe chewing stick or “miswak” has demonstrated growth-inhibitory effects on several oral micro-organisms including Helicobacter pylori (H. pylori). This study explores the effect of miswak on oral H. pylori among fasting and non-fasting subjects. MethodsThis cross-over randomized clinical study included 40 subjects. Twenty subjects were on 12-hour fasting and 20 subjects were not fasting. At baseline (T0), clinical periodontal parameters were recorded, and the participants were instructed on the use of toothbrush alone or toothbrush with miswak in a cross-over manner, for a period of two weeks each. Plaque and salivary samples were collected at T0, after two weeks (T1) and after 4 weeks (T2). Quantification of H. pylori from the plaque and salivary samples were performed by real-time polymerase chain reaction (qPCR). ResultsThere were 28 males and 12 females, and the mean age of the participants was 29.5 ± 7.1 years. At baseline, the median count of H. pylori was 27.61 × 103 cells/mL. The non-fasting group had significantly (p < 0.05) higher quantities of H. pylori, in both the plaque and the salivary samples, as compared with the fasting group. At T0, a statistically significant correlation was observed between the quantities of H. pylori in the dental plaque and selected clinical periodontal parameters (p < 0.05). For non-fasting subjects, a statistically significant reduction in the H. pylori counts was observed in the dental plaque samples on using miswak and toothbrush (p < 0.05). ConclusionNon-fasting subjects showed significant reduction in the H. pylori counts in dental plaque by complementing miswak chewing sticks with toothbrushing.