Health care students often endure numerous stressors throughout their undergraduate education that can have lasting negative effects on their mental well-being. Positive Intelligence (PQ) is a digital mental fitness program designed to enhance self-mastery and help individuals reach their potential by strengthening various "mental muscles." This study aims to evaluate the effectiveness of a 6-week app-delivered PQ program in reducing perceived stress, increasing self-compassion, and decreasing rumination tendencies among health care undergraduates. We hypothesized that students would show reductions in perceived stress, increases in self-compassion, and decreases in rumination tendencies by the end of the PQ program, compared with their preprogram scores. We adopted an exploratory approach for the 5-month follow-up due to the limited research consensus on the sustained effects of app-based programs over varying periods. The PQ program includes weekly hour-long videos, weekly group meetings, and daily 15-minute app-guided practices. Participants were first-year students from the occupational therapy program at a university in Singapore. Participants completed surveys measuring self-compassion, perceived stress, and rumination levels before and after the PQ program, and again at a 5-month follow-up. Data were analyzed using repeated measures ANOVA to assess differences across the pretest, immediate posttest, and follow-up posttest. Out of 87 students enrolled in the study, the final sample consisted of 64 students (n=47, 73%, female; mean age 23 years, SD 5.06 years) with complete data. At the end of the 6 weeks, students exhibited significant increases in self-compassion (before the intervention: mean 3.07, SD 0.35; after the intervention: mean 3.34, SD 0.35; P<.001) and reductions in rumination tendencies (before the intervention: mean 3.57, SD 0.40; after the intervention: mean 3.27, SD 0.34; P<.001). However, no significant change in perceived stress levels was observed (before the intervention: 2.99, SD 0.14; after the intervention: mean 2.97, SD 0.16; P=.50). These effects were not influenced by the daily app-based practice of PQ exercises, and there were no sustained effects on self-compassion (mean 3.17, SD 0.27; P=.09) or rumination tendencies (mean 3.42, SD 0.38; P=.06) at the 5-month follow-up. Additionally, there was a significant increase in perceived stress at follow-up (mean 3.17, SD 0.21; P<.001) compared with pre- and postintervention levels. The PQ program did not directly alter stress perceptions but may have reframed students' automatic negative thought processes, increased their awareness of self-sabotaging behaviors, and enhanced their self-compassion while reducing ruminative thinking. These findings highlight the importance of self-awareness for students' well-being. Students can benefit from practices such as mindfulness and peer discussions to enhance self-compassion and reduce rumination. Educators trained in the PQ program can foster a supportive environment that encourages self-compassion, challenges negative self-talk, and helps students manage stress.