Previous studies have reported the effect of transcranial pulsed current stimulation (tPCS) on eliminating cognitive fatigue, but there is little research on optimizing the intervention program of tPCS. The purpose of this study was to explore the effect of different tPCS intervention programs on the elimination of physical fatigue in college athletes. Accordingly, 40 healthy college athletes were randomly divided into two groups of 20, denoted as A and B. Both groups exercised on treadmills. There were 15 subjects in group A who met the criteria of moderate physical fatigue, and 15 subjects in group B who met the criteria of severe physical fatigue. The subjects in each group were intervened with five different intervention programs of tPCS (intervention programs Ⅰ, II, III, IV and Ⅴ). The heart rate variability (HRV) and concentrations of oxygenated hemoglobin (HbO2) were measured before and after each intervention to judge the elimination effects of different intervention programs on different degrees of physical fatigue; the measurement indicators of the HRV include RMSSD, SDNN, HF and LF. The results indicated that tPCS intervention can eliminate both moderate and severe physical fatigue. Programs II, III, and IV had a significant effect on eliminating the moderate physical fatigue of athletes (p < 0.05), among which program II, with a stimulation time of 30 min and a stimulation intensity of sensory intensity, had the best effect. Programs I, II, III, and IV all had significant effects on eliminating the severe physical fatigue of athletes (p < 0.05), among which program I, with a stimulation time of 30 min and a stimulation intensity of sensory intensity + 0.2 mA, had the best effect. We conclude that different tPCS intervention programs can have different effects on the elimination of physical fatigue. The effects of the five intervention programs on the elimination of physical fatigue in athletes are as follows: program II is most suitable for moderate physical fatigue, and program I is most suitable for severe physical fatigue.