Background: The loss of skeletal muscle mass by aging determines the health status and the quality of life (QoL).

Objective: To examine the relationships between appendicular muscle strength and the QoL of elderly adults in gender difference.

Methods: This was a cross-sectional study, in which 690 subjects who participated in older adults health examination in the health management center of Tri-Service General Hospital from 2018 to 2021. A structured questionnaire was used to collect basic demographic data. The 12-Item Short Form Survey (SF-12) was used to evaluate the QoL of subjects. Their grip strength and gait speed were measured, and Dual-energy X-ray absorptiometry was used to measure muscle mass and other body composition data. Multivariate regression analysis was used to examine the relationships between upper and lower limb muscle strength and the QoL of older adults.

Results: In men, legs muscle mass percentage (LegsMM%) (β = 3.67; 95% CI: 0.64–6.69; p = 0.018) and gait speed (β = 6.09; 95% CI: 3.88–8.30; p < 0.001) were positively associated with physical component summary (PCS) scores, and gait speed (β = 4.63; 95% CI: 2.66–6.60; p < 0.001) was also related to an improvement mental component summary (MCS) scores. In women, arms muscle mass percentage (ArmsMM%) (β = 6.50; 95% CI: 2.34–10.66; p = 0.002) and grip strength (β = 10.54; 95% CI: 6.27–14.81; p < 0.001) had the greatest effect on improving PCS scores, whereas grip strength (β = 7.58; 95% CI 4.00–11.17; p < 0.001) was also found to help improve MCS scores.

Conclusions: Men should focus on lower limb training, whereas females should focus on upper limb training to effectively improve their QoL. Appropriate exercise interventions should be designed for different genders for the promotion of the healthy aging policy.