Objective: To investigate the clinical significance of salivary secretory immunoglobulin A (sIgA), matrix metalloproteinases (MMPs), Streptococcus mutans, and Streptococcus sobrinus in children with dental caries, with a focus on the impact of physical games, fitness, and participation in athletic activities. Methods: From August 2021 to May 2022, 120 children with severe dental caries, diagnosed at our hospital’s oral outpatient department, were selected and categorized into severe (60 cases) and mild (60 cases) caries groups. An additional 60 caries-free children served as controls. Oral examinations were conducted, and the caries loss compensation index was calculated for all participants. Salivary levels of sIgA and MMPs were measured using ELISA, while Streptococcus mutans and Streptococcus sobrinus levels were quantified through qRT-PCR. The study also assessed the relationship between these biomarkers and the children's engagement in physical activities. Results: Caries Loss and Filling Index: Significant increases were observed in the caries loss and filling index in both caries groups compared to controls (P<0.05). sIgA, MMP-2, MMP-9 Levels: Elevated levels of salivary sIgA and MMP-9 in the mild group, and sIgA, MMP-2, and MMP-9 in the severe group were noted compared to controls (all P<0.05). The severe group showed significantly higher levels of sIgA and MMP-2 than the mild group (P<0.05). Streptococcus Mutans and Streptococcus Sobrinus Levels: Both groups exhibited increased levels of these bacteria compared to controls (P<0.05), with significantly higher levels in the severe group versus the mild group (P<0.05). Correlation Analysis: A positive correlation was found between the levels of Streptococcus mutans, Streptococcus sobrinus, sIgA, MMP-2, MMP-9, and the caries loss index (P<0.05). The influence of physical activity on these correlations was also explored. Multivariate Linear Regression Analysis: The biomarkers’ levels significantly predicted dental caries presence, with adjustments for physical activity indicating a potential modifying effect (P<0.05). Conclusions: Increased levels of Streptococcus mutans, Streptococcus sobrinus, sIgA, MMP-2, and MMP-9 in saliva are associated with the occurrence and severity of dental caries in children. This association is further influenced by the children's physical activity levels, suggesting that engagement in physical games, fitness, and athletic activities could modify the risk and impact of dental caries. These findings highlight the importance of considering physical activity in the prevention and management strategies for dental caries in children, particularly those actively engaged in sports.