Objective: This study aimed to investigate the effects of a mental health literacy enhancement program on mental health literacy and levels of depression. Methods: This study employed a quasi-experimental, two-group repeated measures design. The sample consisted of 38 undergraduate students from Udon Thani Rajabhat University, selected through purposive sampling based on inclusion criteria, specifically those with moderate levels of depression. Participants were assigned into experimental and control groups using a matched-pair technique. The experimental group participated in a mental health literacy enhancement program comprising eight sessions, each lasting 60-90 minutes. The control group received training under the Social Engineer Project, which aimed to develop soft skills. Mental health literacy and depression levels were assessed at three time points: pre-intervention, post-intervention, and one-month follow-up. The instruments used included the Mental Health Literacy Scale, and depression screening and assessment tools (2Q and 9Q). Data were analyzed using descriptive statistics and t-tests. Results: The experimental group demonstrated significantly higher mental health literacy than the control group after receiving the program and at the one-month follow-up, with statistical significance at the p < .001 level. Furthermore, the experimental group exhibited significantly lower risk of depression than the control group both post-intervention and at the one-month follow-up, also with statistical significance at the p < .001 level. Conclusion: The mental health literacy enhancement program represents a potential approach for reducing depression among university students and may serve as an alternative strategy for the prevention of depression in this group.