To investigate the effect of caries activity detection combined with fluoride on the prevention of oral caries in preschool children. Methods A total of 50 preschool children admitted to our hospital from June 2019 to June 2022 were selected as the research objects and randomly divided into control group and observation group, with 25 preschool children in each group. The control group was given oral health education prevention, and the observation group was given caries activity detection combined with fluoride prevention. The caries activity risk, new caries prevalence, compliance and oral examination were compared between the two groups. Results The low, medium and high risk rates of the observation group after intervention were lower than those of the control group (P <0.05). The dt, ds, mt, ms, ft, fs, dmft and dmfs in the observation group were lower than those in the control group (P <0.05). The compliance rates of fluoride toothpaste, standard brushing, mouthwash after meals, no eating before bedtime and oral examination in the observation group were higher than those in the control group (P <0.05). The caries rate, the caries rate of severe young children and the detection rate of soft dirt in the observation group were lower than those in the control group (P <0.05). Conclusion Caries activity detection combined with fluoride can effectively reduce the risk and prevalence of dental caries in preschool children, and improve children's awareness and compliance with oral health.