The hardware description of circuits usually contains many loops. Register Transfer Level (RTL) simulation is a critical step to verify the correctness of circuits and is time-consuming. Thus, it is necessary to speed up its process. However, the speedup of existing RTL simulation acceleration techniques is usually small. Although the speedup of hardware acceleration is large, the hardware cost is high. Some methods utilize performance models without performing RTL simulation to obtain rough simulation performance and have large speedup. However, they do not support functional verification. In order to address the problems, we propose a loop-oriented RTL simulation acceleration approach based on code instrumentation for designs synthesized by High-Level Synthesis. Our approach reduces the RTL simulation time by skipping a large number of repeated loop iterations, and maintains high accuracy for the prediction of the number of cycles by reserving some loop iterations. We establish a performance prediction model and an interval value formula for skipping loop iterations. We conduct experiments on the MachSuite benchmark. The results show that for the RTL simulation of single data processing and batch data processing, the average speedup of our approach can reach 7.49× and 43.3×, respectively, and the average prediction errors of the number of cycles are 1.71% and 1.06%, respectively. It also reveals that the interval value obtained by our approach for skipping loop iterations can quickly and effectively balance between the accuracy of prediction of the number of cycles and speedup. Compared to the state-of-the-art approach ESSENT, the speedup of our approach is better and the accuracy of prediction of the number of cycles remains at the same level as that of performance models.