Adults with physical disabilities encounter multifaceted challenges, emphasizing the critical need to address both their physical and psychological well-being while overcoming barriers to physical active participation. Recognizing and addressing these issues is vital for creating inclusive interventions that cater to their specific needs, promoting active engagement, and enhancing overall well-being. This study aimed to investigate the effectiveness of integrating structured exercise and mindfulness techniques in a community-based exercise program tailored for adults with physical disabilities to enhance health-related fitness, self-efficacy, and overall quality of life. Fifteen participants, aged 25–55, with diverse mobility impairments, musculoskeletal conditions, and neurological disorders, participated in a 9-week individualized structured exercise program, involving 90-minute sessions two times weekly. The program focused on improving physical and psychological well-being through combined physical and psychological training. Measurements were assessed at baseline and program completion, covering health-related fitness, self-efficacy, and quality of life domains. Paired t-test and MANOVA revealed substantial improvements in health-related fitness markers, including grip strength and body composition, alongside heightened self-efficacy, and improvements across multiple quality of life domains compared to pretest measures. These improvements were statistically significant (p < 0.05) and demonstrated a moderate effect size on average (Cohen’s d = 0.5–0.8) across the assessed variables. Pearson correlation analysis indicated grip strength and fat mass had a significant correlation with quality of life (p < 0.05). Future research should include larger, controlled studies, as the lack of a control group and small sample size limit conclusions, yet the integration of structured exercise and mindfulness techniques in a community-based exercise program showed promising outcomes for enhancing the physical and psychological well-being of adults with physical disabilities, underscoring its potential significance in disability and rehabilitation studies.