The oral probiotic Streptococcus salivarius M18 (S M18) offers the potential to confer oral health benefits as it produces bacteriocins which are targeting Streptococcus mutans. The purpose of this clinical trial was to assess the effect of S M18 probiotics on salivary S. mutans and to identify the correlation between dental caries with salivary S. mutans count. This clinical trial was conducted in 40 children between the age-group 3-6 years, subjects were randomly selected and the decay extracted filled (due to caries) (def score) was recorded. The presalivary unstimulated saliva was collected and subjected to microbiological examination for S. mutans counts, salivary pH, and buffering capacity. Children were divided into two groups as the control and the experimental group. bacteriocin like inhibitory substances M18 (M18 is a strain number) (BLIS M18) probiotic was administered in the experimental group, and unsweetened lozenge as a placebo in the control group for 7 days and postsalivary samples were collected and subjected to microbiological examinations for S. mutans count, salivary pH, and buffering capacity. A significant decrease in the S. mutans counts were noticed, an increase in buffering capacity, and no significant change in pH was observed after the intervention of S M18. A linear correlation was observed between the def score and S. mutans count. This clinical trial revealed that S M18 in its 7 days regime can lead to the inhibition of S. mutans counts favorably in the oral cavity by affecting salivary pH and buffering capacity. Salim HP, Mallikarjun SB, Raju S, et al. Randomized Clinical Trial of Oral Probiotic Streptococcus salivarius M18 on Salivary Streptococcus mutans in Preprimary Children. Int J Clin Pediatr Dent 2023;16(2):259-263.