Background: This study aimed to examine the effects of a 12-week multicomponent mobile app-delivered intervention, the Meru Health Program (MHP), on mental health quality of life (QoL) and loneliness among the middle-aged and older adults with depression symptoms.Methods: The eligible participants (M age = 57.06, SD = 11.26 years) were enrolled in the MHP, a therapist-supported mobile intervention. Using a non-randomized pre-post design, change in mental health QoL [WHO QoL Brief (WHOQOL-BREF) psychological health] and loneliness (UCLA Loneliness Scale) from baseline to post-treatment were examined. Time of enrollment [pre- vs. post-coronavirus disease 2019 (COVID-19)] was included as a between-subjects factor in the repeated measures analyses.Results: Forty-two participants enrolled prior to the COVID-19 pandemic; eight enrolled after the pandemic began. Among the pre-COVID-19 enrollees, increase in mental health QoL, F_{(1, 38)} = 12.61, p = 0.001, η² = 0.25 and decreases in loneliness emerged, F_{(1, 38)} = 5.42, p = 0.025, η² = 0.13. The changes in mental health QoL, but not loneliness, held for the combined sample, such as post-COVID-19 enrollees, F_{(1, 44)} = 6.02, p = 0.018, η² = 0.12. The regression analyses showed that increases in mindfulness were associated with the increased mental health QoL and decreased loneliness.Conclusion: Therapist-supported digital mental health interventions, such as the MHP, have the potential to improve mental health QoL and decrease loneliness among the middle-aged and older adults. The findings for loneliness may not hold during the periods of mandated isolation. Instead, therapists supporting digital interventions may need to tailor their approach to target loneliness.