background: Childhood caries, a prevalent chronic disease, affects 60-90?% of children in industrialized regions, leading to lesions in both primary and permanent teeth. This condition precipitates hospital admissions, emergency room visits, elevated treatment costs, and missed school days, thereby impeding the child's academic engagement and increasing the likelihood of caries into adulthood. Despite multiple identified risk factors, significant interpersonal variability remains unexplained. The immune system generates a unique antibody repertoire, essential for maintaining a balanced and healthy oral microbiome. Streptococcus mutans is a primary contributor to the development of caries. methods: Employing mass spectrometry, we investigated the S. mutans proteins targeted by antibodies in children both with and without caries, delineating a fundamental suite of proteins discernible by the immune systems of a majority of individuals. Notably, this suite was enriched with proteins pivotal for bacterial adhesion. To ascertain the physiological implications of these discoveries, we evaluated the efficacy of saliva in thwarting S. mutans adherence to dental surfaces. results: Antibodies in most children recognized a core set of ten S. mutans proteins, with additional proteins identified in some individuals. There was no significant difference in the proteins identified by children with or without caries, but there was variation in antibody binding intensity to some proteins. Functionally, saliva from caries-free individuals, but not children with caries, was found to hinder the binding of S. mutans to teeth. These findings delineate the S. mutans proteome targeted by the immune system and suggest that the inhibition of bacterial adherence to teeth is a primary mechanism employed by the immune system to maintain oral balance and prevent caries formation. conclusions: These findings enhance our knowledge of the immune system's function in oral health maintenance and caries prevention, shedding light on how immunoglobulins interact with S. mutans proteins. conclusions: Targeting S. mutans proteins implicated in bacterial adhesion could be a promising strategy for preventing childhood caries.