Doped DLC film is expected to be a vital surface protection material in aerospace and other important fields. However, the long experiment cycle for screening efficient dopants, premature failure caused by high residual stress, and insufficient understanding of the microscopic mechanism, seriously limit its further improvement. In this work, the performance prediction and mechanism study of doped DLC films were proposed by combining molecular dynamics (MD) and first-principles calculations, and the commonly used Si and MoS2 were selected as the typical elemental and compound dopants for investigations, respectively. MD was used to evaluate the influence of both the type of dopant and its amount on the structure and properties, including the content of sp2-C and sp3-C, hardness, elastic modulus, and friction coefficient of DLC films. First-principles calculations were performed to study the modification mechanism of Si and MoS2 dopants from a viewpoint beyond the experimental scale. This study was verified by experimental investigation and proven to make a fast prediction and screening for the doping craft of DLC films.