Institutionalized older adults have limited ability to engage in horticultural activities that can improve their physical and mental health. This study explored the effects of a combination of 3D virtual reality and horticultural therapy on institutionalized older adults' physical and mental health. The study used a quasi-experimental design. A total of 106 older adults from 2 long-term care facilities were recruited and assigned to the experimental (n=59) or control (n=47) group. The experimental participants received a 9-week intervention. Both groups completed 3 assessments: at baseline, after the intervention, and 2 months later. The outcome variables included health status, meaning in life, perceived mattering, loneliness, and depression. The experimental group demonstrated significantly improved health status (P<.001), meaning in life (P<.001), and perceived mattering (P<.001) as well as significantly reduced depression (P<.001) and loneliness (P<.001) compared to the control group immediately after the intervention; these effects persisted for up to 2 months. This study verified the beneficial effects of a combination of 3D virtual reality and hands-on horticultural therapy on older adults' health. These results could support the future successful implementation of similar programs for institutionalized older adults on a larger scale.