An experimental study was conducted to investigate the influence of mainstream oscillations on spatio-temporal variation of leading-edge film cooling effectiveness. The investigation utilized fast-response pressure-sensitive paint (Fast-PSP) technique at high frame rate. During the experiment, coolant (i.e., CO2, DR = 1.53) was discharged into three rows of cylindrical holes. Various blowing ratios (i.e., M = 0.50, 0.75, 1.00, and 1.50) were tested under the steady (i.e., f = 0 Hz) and oscillating (i.e., f = 7 Hz and 25 Hz) conditions. The measured instantaneous effectiveness was analyzed in terms of time-averaged and phase-averaged results. The results revealed that the mainstream oscillation, consisting of simultaneous pressure and velocity oscillation, significantly influences the behavior of the film cooling effectiveness. The time-averaged effectiveness significantly decreased at high oscillating frequency (i.e., 13.0–19.8% reduction at M = 0.50, f = 25 Hz compared with f = 0 Hz), especially at low blowing ratios (i.e., M = 0.50 and 0.75). The phase-averaged results captured significant decay in the film distributions associated with backflow caused by negative pressure gradients in coolant holes at certain phases. However, the mainstream oscillation effect was relatively insignificant at high blowing ratios (i.e., M = 1.00 and 1.50), which revealed the robustness of coolant coverage at low coolant Strouhal number (i.e., high blowing ratio) under the same oscillating frequency. Furthermore, the unsteady coolant intermittency showed highly unstable film coverage at high coolant Strouhal number. The coolant decay associated with backflow at high coolant Strouhal number should be considered by the gas-turbine designers in order to improve the lifecycle of turbine blades.