Based on experiments, a numerical analysis is used to quantitatively explore the influence of coal and surfactant microstructures on wettability. First, based on an infrared spectrum experiment, the distribution of oxygen-containing functional groups, aromatic hydrocarbons, and aliphatic hydrocarbons of coal and surfactants was obtained. Second, the wettability relationship between coal and different surfactants was determined by optical titration, and the coal dust wettability and surfaces were optimized. The key factors of the active agent wetting ability affecting lignite wetting mainly depend on the carbonyl, ether, and carboxyl groups in the surfactant. The factors affecting non-stick coal and gas coal wetting mainly depend on the ether group and aromatic amine in the surfactant. The factors affecting fat coal wetting mainly depend on the ether group and hydroxyl group in the surfactant. Finally, the factors affecting coking coal and anthracite wetting mainly depend on the surfactant ether group, aliphatic amine, and aromatic amine. Then, combining the structural parameters with the coal wetting results, the quantitative mathematical relationship between coal dust wettability, the important influencing factors of the surfactant, and the wettability index was established. Finally, a perfect and reasonable wettability evaluation model between coal and the surfactants was established. The relative activity of methyl ether and aromatic ether is greater than that of methyl ether, and the influence on the lignite, coking coal, and anthracite wettability conforms to the model . The influence on the non-caking coal and fat coal wettability conforms to the model , while the influence on the gas coal wettability conforms to the model Z = A + B1X1 + B2X2. In general, this study provides scientific guidance for the compounding of high-efficiency and environmentally protective composite dust suppressors to realize clean mine production.