At present, the use of hydrotalcite-like materials to remove fluoride from water is a relatively popular research topic. Herein, an experimental and theoretical study on the adsorption of F⁻ on the surface of hydrotalcite was reported. The experiments indicate that adsorption reached equilibrium in 2 minutes. The experimental results of adsorption thermodynamics show that adsorption is spontaneous and endothermic. Calculations based on Density Functional Theory (DFT) and Molecular Dynamics (MD) simulation were used to research the adsorption of F⁻ on the (0 0 3) crystal face of Cl⁻-hydrotalcite. The optimal geometric configuration of the adsorption of F⁻ on different sites of the hydrotalcite surface was established. F⁻ has the lowest adsorption energy (−300.565 kJ mol⁻¹) at the vacancy above the aluminum atom and this configuration is the most stable. The analysis of the HOMO and LUMO and Fukui function results show that F⁻ is more susceptible to electrophilic attack and adsorbed on the surface of hydrotalcite than Cl⁻. The calculation results of charge population and Partial Density Of States (PDOS) show that electron transfer occurred between F⁻ and H on the surface of hydrotalcite laminates, and the strong hybridization of the F⁻ 2p orbital with the H 1s orbital on the surface shows the formation of hydrogen bonds between them. The simulation results of adsorption thermodynamics are the same as the experimental results and the correctness of the experiment is verified. Finally, MD simulation was carried out to explain the effect of water on adsorption and confirmed the bonding mechanism.