During the COVID-19 pandemic, the world population suffered from a range of mental health problems, and there has been a need for new community-based psychosocial interventions. This study aimed to investigate the effectiveness and feasibility of Natural-Based Therapy (NBT) for the community experiencing psychological distress during the pandemic. A multi-site trial comparing NBT and control groups was conducted. In total, 291 participants with mild to severe depression or anxiety were recruited from 11 sites in Korea. A total of 192 participants participated in 30-sessions therapeutic gardening, and 99 remained in the control group. Mental health and well-being were assessed using seven measures of depression, anxiety, daily activity, life satisfaction, mindfulness, stress, and loneliness. The effect sizes (Cohen’s d) were medium to large: depression (0.583), anxiety (0.728), daily activity (1.002), life satisfaction (0.786), mindfulness (0.645), stress (0.903), and loneliness (0.695). Multilevel analysis showed significant interaction effects in the Time × Group for all measures. The results of the Pearson correlation analysis indicated that changes in all variables correlated significantly with each other, with moderate to large effect sizes. Therapeutic alliance at post-test moderated intervention outcomes. We concluded that NBT is a promising psychosocial intervention for treating psychological distress for community dwellers.