Introduction: Interproximal Reduction (IPR) or reproximation of enamel is of prime importance in orthodontics for correcting arch length-tooth size discrepancies. Despite its widespread application, IPR has been associated with adverse effects on the enamel surface. Aim: The aim of this study was to investigate whether laser application, when combined with fluoride application, enhances the remineralisation potential of enamel. Materials and Methods: This in-vitro study was conducted at Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India, from December 2021 to July 2022. It involved 54 extracted teeth, divided into three groups of 18 samples each. Reproximation of 0.25 mm was performed on the proximal enamel surface of each tooth. Group 1 served as the control, group 2 was subjected to Fluor Protector, and group 3 received low-level laser therapy (Er,Cr:YSGG) after Fluor Protector application. Fluor Protector (Ivoclar Vivadent) was applied for seven days. Following the seven-day fluoride administration, a laser treatment using 0.75 W of power and 8.5 J/cm2 of energy was applied for 20 seconds. Microhardness testing was conducted on the samples using a Vickers Hardness Tester. All specimens underwent surface topographic analysis with Scanning Electron Microscopy (SEM) and were evaluated for mineral content (% weight) using SEM-Energy Dispersive X-Ray analysis (EDX). Paired t-tests were performed to compare the pre- and post-microhardness values, while one-way Analysis Of Variance (ANOVA) test and Tukey’s Post-hoc test were used to compare the microhardness values between the groups. Results: The mean microhardness values recorded for group 1, group 2, and group 3 were 209.4±18.4 N/mm2 , 215.16±21.0 N/ mm2 , and 233±18.05 N/mm2 , respectively. ANOVA test revealed a significant difference in microhardness values between group 1 and group 2 (p-value=0.004), as well as between group 1 and group 3 (p-value=0.001). The microhardness value was highest for group 3, followed by group 2 post-intervention. SEM analysis showed that laser-treated enamel surfaces were smoother, with well-coalesced enamel rods. The porous structure of enamel was lost due to fluoride deposition in group 2 and group 3, resulting in a smooth surface. Conclusion: The combined application of fluoride and laser therapy demonstrated synergistic effects in remineralising the slenderised enamel. This simple, non-invasive technique may benefit patients undergoing IPR procedures by reducing the occurrence of dental caries.