Aims: Physical activity increases and maintains bone mineral density (BMD) and reduces the risk of bone fractures. Several factors may affect quality of life (QoL) in postmenopausal osteoporosis (PMO). This study aimed to evaluate the effect of physical activity level on QoL in women with PMO. Methods: Demographic and clinical characteristics were recorded in this cross-sectional study. Physiological parameters, including handgrip strength (HGS), one-leg standing time, and ability to squat down on the floor, were collected. The BMDs at L1–L4 total, femur neck (FN), and femur total (FT) were measured by dual-energy X-Ray absorptiometry device. Physical activity level was calculated as metabolic equivalent of task (MET) value using the International Physical Activity Questionnaire (IPAQ) and patients were classified as ‘low, moderate and high’. The European Osteoporosis Foundation Quality of Life Questionnaire (QUALEFFO-41) was used to evaluate QoL. Results: This study included 179 postmenopausal women with a mean age of 62.72±7.83 years. The average values of HGS and one-leg standing time were determined as 24.6±8.1 kg and 17.6±27.6 seconds, respectively. According to the IPAQ categories, 66.5% of the participants had low level of physical activity, and the median IPAQ score was 2286 MET. The mean QUALEFFO-41 total score was found to be 46.2±17.6. All QUALEFFO-41 questionnaire subscores, IPAQ categories, and IPAQ MET scores were significantly correlated with one-leg standing time. Additionally, all QUALEFFO-41 questionnaire subscores were negatively correlated with the HGS but positively correlated with the IPAQ category. All subscores of QUALEFFO-41 were significantly higher in inactive patients, indicating a worse QoL. Conclusion: Low physical activity levels in women with PMO negatively impact their QoL. Additionally, physical activity level correlates with muscle strength and balance. Thus, interventions to increase muscle strength, balance and physical activity levels should be included in the treatment to improve patients’ QoL with PMO.