Ketoprofen is a poorly-water soluble drug. To improve the solubility and dissolution rate of ketoprofen, previous experiments developed Ketoprofen-Polyethylene glycol binary solid dispersion system, Ketoprofen-Polyethylene glycol-Tween 60 and Ketoprofen-Polyethylene glycol-Sodium dodecyl sulfate ternary solid dispersion systems. In the ternary solid dispersion systems, the additive of a nonionic surfactant Tween 60 or an anionic surfactant Sodium dodecyl sulfate could effectively improve the dissolution rate of Ketoprofen than binary ones. However, the dissolution mechanism of binary and ternary solid dispersions is still unclear concerning the molecular aspect. Thus, the research aimed to investigate the molecular dissolution mechanism of both binary and ternary solid dispersions by molecular dynamics simulations. The simulated annealing method was performed to simulate the preparation of solid dispersions, and the dissolution processes were simulated by molecular dynamics. The simulation results indicated that drug molecules in ternary systems were easier to be released into the water than that of binary one. Moreover, the additive of Sodium dodecyl sulfate in the system had better effects than the system with Tween 60. These modeling results were in well agreement with the experimental results. For the binary and the ternary solid dispersions, the additional surfactants can improve the wettability of the drug molecules and the structure of the random coils, which can help the drug molecules to escape from the system easily. Different molecular structures and charges between Sodium dodecyl sulfate and Tween 60 influenced the behavior of the systems. The shorter chain of Sodium dodecyl sulfate molecule may contribute to the good effect of ternary system. One the other hand, the charge of Sodium dodecyl sulfate molecule may also prevent the re-aggregation of the systems. This research presented reasonable explanation about the molecular dissolution mechanism of both binary and ternary solid dispersions. Our research will also benefit pharmaceutical scientists to develop the formulations of solid dispersions.