Previous online mindfulness-based interventions for burnout and stress reduction in medical personnel had limited effect size and high dropout rate, so we developed a new online mindfulness program ‘Mindful Senses (MS)’ with aims to increase effect size and lower dropout rate. To test its efficacy and feasibility, ninety medical personnel with moderate or high levels of burnout and stress from across Thailand were recruited and randomly allocated into Group A and Group B equally. Group A read psychological self-help articles (PSA) and attended MS program through smartphone application during weeks 1–4. Group B read PSA during weeks 1–4 and attended MS program during weeks 9–12. Burnout, stress, anxiety, depression, mindfulness, and quality of life were measured at baseline, week 4, and week 8 for both groups, and at weeks 12 and 16 for Group B. Group x time interaction was analyzed by repeated-measures ANOVA. The results showed that, compared to PSA only, MS + PSA had statistically significant improvement of burnout, stress, anxiety, depression, mindfulness, and quality of life with moderate-to-very large effect sizes at week 4 (d = 1.33, 1.42, 1.04, 1.14, 0.70, and 1.03, respectively) and moderate-to-large effect sizes at week 8 (d = 0.84, 0.98, 0.73, 0.73, 0.66, and 0.94, respectively). The dropout rate was 4.4%. In conclusion, the MS program has potential to be an alternative intervention for medical personnel suffering from burnout and stress.