Modern toothbrushes origin can be traced to plant-derived chewing sticks, which were documented to be used Babylonians as early as 3500 BC. Chewing sticks are routinely used for cleaning teeth in Asia, Africa, South America, and the Middle East. The aim of the current study was to evaluate the antibacterial effect of miswak herbal toothpaste compared to fluoride toothpaste using a normal toothbrush, against Streptococcus mutans in high caries risk patients.A total of 32 participants were recruited to the current clinical trial using convenience sampling randomly either to miswak or fluoride toothpastes groups (n=16). The bacterial count represented as colony-forming units per milliliter (CFU/ml) was assessed at baseline and after 1 week, 1 month and 3 months. Moreover, the ion release for silicone, calcium, phosphorus, and fluoride from both toothpastes was analyzed in addition to the pH of both toothpastes and their supernatants. Intergroup comparison was performed using independent t test, while intragroup comparison was performed using repeated measures ANOVA followed by tukey post-hoc test and paired t test when appropriate.There was no statistically significant difference between both toothpastes for the S. mutans count within each follow up period, however the bacterial count significantly decreased over time in both groups. Signal Fluoride toothpaste exhibited statistically significant higher ion release when compared to the Dabur Miswak toothpaste. There was no statistically significant difference between either toothpastes regarding pH (P = 0.5368), while comparison between supernatants of toothpastes have shown statistically significant difference (P = 0.0194), with a higher pH in miswak toothpaste.Miswak herbal toothpaste possesses a potent antibacterial effect, yet its remineralization potential is questionable due to its inferior ion release that will affect the ion substantivity in saliva, which is an important factor in remineralization.