Objectives <p>In recent years, mindfulness-based interventions conducted as part of a class have focused on supporting the psychological functioning of university students. This study aimed to examine the effect of a 5-week physical exercise–based mindful self-compassion (PEMSC) intervention on university students’ interoceptive awareness, behavioral regulations in exercise, emotional reactivity, and self-generated stress levels.</p> Method <p>This quasi-experimental study involved an experimental group (5-week PEMSC), an active control group (5-week Mindfulness-Based Stress Reduction (MBSR)), and a passive control group. The participants were 135 students (<i>M</i>_age = 19.44) from the Faculty of Health Sciences (physiotherapy and rehabilitation, midwifery, nutrition, and dietetics) and the Faculty of Dentistry.</p> Results <p>Both PEMSC and MBSR intervention programs were associated with significant improvements in participants’ interoceptive awareness (<i>η</i>^<i>2</i><i>ₚ</i> = 0.548, <i>p</i> &lt; 0.001), as well as reductions in emotional reactivity (<i>η</i>^<i>2</i><i>ₚ</i> = 0.626, <i>p</i> &lt; 0.001) and self-generated stress (<i>η</i>^<i>2</i><i>ₚ</i> = 0.446, <i>p</i> &lt; 0.001) over time, suggesting broadly comparable patterns of change. Participants in the PEMSC group exhibited more favorable patterns of change in internal exercise-related behavioral regulation (<i>η</i>^<i>2</i><i>ₚ</i> = 0.597, <i>p</i> &lt; 0.001) than those in the MBSR and control groups did. Furthermore, Latent Growth Curve Modeling indicated that the PEMSC intervention yielded more stable, continuing trajectories of improvement (evidenced by significant quadratic growth parameters). The quadratic LGCMs had smaller DIC and BIC values and posterior predictive <i>p</i>-values around 0.30, indicating a better fit. These results point to potentially distinct overall influences of the two programs on the regulation of physical exercise behavior, while warranting cautious interpretation given the quasi-experimental design.</p> Conclusions <p>Programs that combine class-based mindfulness interventions with physical exercise may be beneficial for higher education students. This study demonstrates that the PEMSC approach offers a promising and time-efficient method for improving university students’ psychological well-being and highlights its potential as an accessible intervention program in higher-education settings.</p> Preregistration <p>This study was not preregistered, and no preregistration record is available.</p>