Objective: To explore the influence of exercise prescription and mobile APP for health education on the physical self-esteem and mental health among female college students,and to provide a reference for improving the level of their mental health. Methods: A stratified random cluster sampling survey was conducted in Tongren university among female freshmen and junior students. Physical Self-esteem Scale and the SCL-90 Scale were used before and after a 4-month exercise prescription and mobile APP for health education among 233 female college students. Results: After intervention, the intervention group had significant higher scores in physical status (14.82±2.37), physical quality (14.36±2.42), motor skill (14.11±2.54), bodily appealing (15.33±2.86) and physical self-worth (15.58±2.72) compared with the control group (t=4.87, 4.51, 4.65, 4.67, 4.10, P<0.05). Somatization symptom (1.37±0.35), interpersonal sensitivity (1.73±0.49), depression (1.67±0.49) and anxiety (1.47±0.46) was significantly improved in the intervention group (t=2.01, 2.01, 2.12, 2.08, P<0.05). Body mass index (BMI) (22.38±2.82) kg/m2 of the intervention group was lower than the control group(23.57±3.08)kg/m2(t=4.40,P<0.05). The intervention group reported longer exercise duration (1.66±0.81) and exercise time (3.61±1.74) compared with the control group (t=-4.66，-5.28,P<0.01). Conclusion The exercise prescription and mobile APP for health education can improve physical self-esteem and mental health, reduce sedentary behavior and increase the exercise duration and exercise time among female college students.