Flotation tests were conducted on a low-grade refractory fluorite ore from Guizhou using tannin and sodium humate as carbonate depressants. The depressant effects of tannin and sodium humate in the flotation of carbonate-bearing fluorite ores were also investigated. The results showed that the mixed depressant of tannin and sodium humate had good depressant effect on carbonate under weak alkaline conditions. Through primary roughing, primary sweeping and flotation of four-stage concentrate of fluorite ore, qualified fluorite concentrate CaF2 with grade of 95.52% and recovery of 91.20% was obtained. Sodium humate has a good selective depressant effect on calcite. Tannic acid inhibits both fluorite and calcite. However, the selective depressant ability of tannins was best in the pH range of 6 to 8. Sodium humate and tannins are chemisorbed on mineral surfaces, and their adsorption capacity on calcite surfaces is greater than that of fluorite. The reaction products of sodium humate, tannin and calcium ions in solution interact with the organic compounds adsorbed on the calcite surface, forming a multilayer adsorption on the calcite surface and making the calcite more hydrophilic. Based on the density flood theory, Materials Studio ( MS) was used to calculate the relevant adsorption energies, and the results were obtained as follows: a. Compared to fluorite, tannin molecules and sodium humate molecules are more easily adsorbed on calcite surface; b. Compared to calcite alone, tannin molecules or sodium humate molecules adsorbed while the adsorption state will be more stable, and tannin and sodium humate synergistically inhibit calcite more effectively than the effect of depressant alone is better.