This study conducted a large eddy simulation (LES) to predict the flow structure and effectiveness of film cooling in a gas turbine. The study focused on a forward expansion hole on a flat plate with an inclined injection angle of 35° and spanwise injection angles (orientation angles) of 0° and 30° under main flow oscillation. In gas turbines, the mainstream flow can exhibit unsteadiness owing to stator–rotor interactions or freestream turbulence. Here, sinusoidal functions are used to approximate the flow oscillations, and their effects are evaluated at frequencies of 0, 8, and 32 Hz, corresponding to Strouhal numbers of 0, 0.603, and 2.413, respectively. The study aims to characterize the film cooling at two time-averaged blowing ratios: 0.5 and 1.0. The range of Strouhal numbers considered in this study is relevant to actual transonic gas turbines. The computational results obtained through LES are validated using experimental data and compared with the Reynolds-averaged Navier–Stokes simulation results. The findings demonstrate the efficiency of LES to predict accurately the distribution of spanwise film cooling effectiveness and spanwise-averaged effectiveness for forward expansion holes on turbine blades under flow oscillations. Comprehensive analyses of various aspects such as the instantaneous turbulent structures of the film cooling flow fields, time-averaged temperature, and root-mean-squared values of the coolant temperature and a proper orthogonal decomposition analysis for velocity vectors are performed. The results show that when the oscillation frequency of the main flow varied from 0 Hz to 32 Hz for a time-averaged blowing ratio of 0.5, the film cooling effectiveness for the forward expansion hole reduced significantly. However, when the frequency increased under a time-averaged blowing ratio of 1.0, the film cooling effectiveness for the hole was only slightly affected by the oscillations. Moreover, an orientation angle of 30° enhanced the film-cooling performance even under flow oscillations. Thus, this paper reports the development of highly effective film-cooling strategies that can guide researchers aiming to mitigate the adverse effects of flow oscillations, thereby enhancing the reliability and efficiency of gas turbine engines.