The present study aimed to examine the effectiveness of life skills training on internalized shame and perceived stress among university students. This research was conducted using a quasi-experimental design with a pretest–posttest control group and a two-month follow-up. The study population consisted of students at the Islamic Azad University, Shiraz Branch, in 2024, from whom 72 participants were selected through convenience sampling and randomly assigned to experimental and control groups (36 in each group). The research instruments included the Internalized Shame Scale (Cook) and the Perceived Stress Scale (Cohen). The experimental group received life skills training based on Kleinke’s protocol in 10 weekly sessions of 45 minutes, while the control group received no intervention. Data were analyzed using repeated measures analysis of variance. The results indicated that life skills training led to a significant reduction in internalized shame and perceived stress in the experimental group compared to the control group (p < 0.05), and these effects were maintained at follow-up. The findings suggest that life skills training is an effective educational and preventive intervention for improving mental health indicators among university students and can be incorporated into student mental health promotion programs.