Objectives: Mental health first aid (MHFA) may have beneficial effects on the public's knowledge, attitude, and behavior; however, its effectiveness in increasing mental health literacy on college students remains unknown. Methods: We systematically searched the PubMed, EMBASE, and Cochrane Library databases from inception to January 2020. We included trials that compared the effect between the MHFA program group and control group on the knowledge, stigmatizing attitudes, confidence, and intention of college students. A random-effects model was used. Results: We analyzed five trials involving 1134 participants and found that the MHFA program could significantly increase the student's knowledge (SMD: 0.49, 95% CI: [0.28-0.70]) and confidence (SMD: 0.71, 95% CI: 0.24-1.19). Conclusions: Overall, the MHFA program could increase college students' knowledge regarding mental health and confidence to support people with mental health problems. However, well-designed control trials are required to investigate the program's effect on mental health literacy in college students.