Abstract: To improve the wetting effect of surfactants on coal dust, the influences of three compound systems, namely anionic + nonionic, anionic + cationic, and cationic + nonionic surfactants, on the wettability of coal dust were investigated through experiments and molecular dynamics simulations, and the droplet size distribution was also studied. The results show that the compound surfactants exhibit either synergistic or antagonistic effects compared with the two single surfactants in the combination. Based on the analysis of synergistic effects, three types of compound systems were optimized using the spreading work index: anionic + nonionic system of sodium secondary alkyl sulfonate + alkyl polyglycoside (SAS-60+APG), anionic + cationic system of sodium alcohol ether sulfate + cetyltrimethylammonium chloride (AES+CTAC), and cationic + nonionic system of dodecyltrimethylammonium chloride + alkyl polyglycoside (DTAC+APG). In-depth research on the coal dust wetting performance of these systems was carried out. The AES+CTAC system has the lowest surface tension and contact angle, but shows a long coal dust settling time and poor wetting ability. The main reason is that after the two single molecules dissociate into anions and cations in solution respectively, the residual groups attract each other to form a denser adsorption layer at the gas-liquid interface. This adsorption layer promotes easier spreading of the liquid, resulting in lower surface tension and contact angle. The SAS-60+APG system has the shortest coal dust settling time of 104 s for complete settlement, indicating the strongest wetting effect on coal dust. In the droplet size test, the D₅₀ and D₉₀ of the DTAC+APG system are the smallest. The D₉₀ of the SAS-60+APG system is close to that of DTAC+APG, but its D₅₀ is significantly larger. This is because the long hydrophobic carbon chain of SAS-60 increases the volume of single micelles in the solution and enhances the steric hindrance effect, making it difficult for the solution to be dispersed into small droplets. The droplet sizes of both systems are much smaller than those of water and AES+CTAC, which is beneficial to collision and settlement with coal dust. Molecular dynamics (MD) simulation results further show that in the SAS-60+APG mixture, surfactant molecules exhibit the strongest attraction to water molecules, promoting the formation of hydrogen bonds and van der Waals forces among water molecules, surfactant molecules and coal molecules. This allows more water molecules to adsorb on the coal surface, increases the coal–water overlapping area, and weakens the disordered motion of water molecules, exhibiting better wettability toward coal dust.