Objective: To investigate the effect of Clinpro? XT Varnish on enamel hardness and enamel demineralization and remineralization during orthodontic treatment. Methods: 27 patients with permanent dentition malocclusion who needed fixed orthodontic treatment were selected. They were divided into control group (fluoride varnish, n=12) and observation group (Clinpro? XT Varnish, n = 15) according to the treatment of tooth surface. The enamel hardness, enamel demineralization index (EDI) and incidence of demineralization were compared between the two groups. Results: The enamel hardness of the two groups increased with time. The enamel hardness of the observation group at 3 months and 6 months after intervention was higher than that before intervention (P<0.05). The enamel hardness of the observation group at 6 months after intervention was higher than that of the control group (P<0.05). The EDI values of the observation group and the control group showed a downward trend with time (P<0.05). At 6 months after intervention, the EDI value in the observation group was lower than that before intervention, 3 months after intervention and in the control group (P<0.05). Additionally, the incidence of enamel demineralization was lower in the observation group than in the control group (P<0.05). Conclusion: Clinpro? XT Varnish can improve the hardness of early demineralized enamel and reduce the recurrence of enamel demineralization, which can replace the intervention of infiltration resin in enamel demineralization during orthodontic treatment.