To investigate the therapeutic effect of resin infiltration combined with fluoride therapy in the repair of early enamel caries. Methods From January 2021 to January 2023, 100 patients who received early enamel caries repair treatment in Affiliated Stomatological Hospital of Guizhou Medical University were selected as the research objects. They were divided into control group and study group by random number table method, with 50 patients in each group, and all of them were 50 teeth. The control group was treated with resin infiltration, and the study group was treated with resin infiltration and fluoride therapy. The clinical efficacy, enamel microhardness value, calcium dissolution and treatment satisfaction were compared between the two groups. Results The total effective rate of treatment in the study group was 100.00%, which was higher than 90.00% in the control group, and the difference was statistically significant (P <0.05). The microhardness of enamel in the study group was higher than that in the control group at 1 and 3 months after operation, and the difference was statistically significant (P <0.05). The calcium dissolution of the study group was lower than that of the control group at 1, 3 d and 1 week after operation, and the difference was statistically significant (P <0.05). The treatment satisfaction of the study group was 98.00%, which was higher than 86.00% of the control group, and the difference was statistically significant (P <0.05). Conclusion The combined treatment of resin infiltration and fluoride has a good effect in the repair of early enamel caries, which can improve the microhardness value of enamel, reduce the risk of demineralization, and patients have higher satisfaction with treatment.