BACKGROUND Physically disabled people experience more restrictions in social activities than healthy people, which are associated with lower level of well-being and poor quality of life (QoL). METHODS A cross-sectional study was conducted. METHODS This study was investigated on among 302 eligible physically disabled people. The predictive role of the demographics and clinical characteristics, anxiety and depression, physical activity, and self-efficacy on the 36-Item Short Form Health Survey (SF-36) was examined. METHODS Statistical analysis used univariate and multivariate regression models. RESULTS Gender, self-reported physical activity levels, use of the disability aid tools, and depression were significantly predictors of the physical component summary (PCS) (R2 = 0.20, P < 0.001). We realized that anxiety, depression, and self-efficacy could significantly predict the mental component summary (MCS) (R2 = 0.43, P < 0.001). CONCLUSIONS Study results revealed that four and three variables could predict 20% and 43% of PCS and MCS variations, respectively. These findings warranted the detection of QoL risk factors and establishment of targeted interventions to optimize the health-related QoL among physically disabled people.