A massive amount of coal gangue (an accompanying solid waste) is produced during coal mining and washing processes, leading not only to the wastage of land resources but also to environmental impacts. Due to the abundant presence of metal oxides such as Fe2O3 and Al2O3 in coal gangue, the extraction of iron and aluminum from it serves as a crucial pathway for the resource utilization of coal gangue. In this study, a thermal activation-acid leaching method was used to extract Fe3+ and Al3+ from coal gangue. Through single-factor experiments, with variables including liquid-to-solid ratio, acid concentration, acid leaching time, and acid leaching temperature, the influence of these factors on the leaching rates of Fe3+ and Al3+ was investigated. Subsequently, response surface optimization experiments were conducted using Design-Expert 13 and Box-Behnken methods, and a regression model with a high fitting degree was established. The results of the regression model indicated that the optimal conditions for leaching Fe3+ and Al3+ were as follows: Acid leaching temperature of 91.71 ℃, acid concentration of 2.84 mol·L−1, liquid-to-solid ratio of 5.90∶1 mL·g−1, and acid leaching time of 3.04 h. Under these conditions, the leaching rates of Fe3+ and Al3+ were 66.039% and 35.844%, respectively. These findings provide a valuable reference for the resource utilization of coal gangue.