Objectives: This cross-sectional study, conducted as part of the Bushehr Elderly Health program stage II in Bushehr, Iran, aimed to evaluate health-related quality of life (HR-QoL) in individuals aged ≥ 60 with osteo sarcopenia, a condition characterized by the co-occurrence of osteopenia/osteoporosis and sarcopenia. Given the increasing elderly population worldwide, understanding the HR-QoL of this demographic is crucial, with osteosarcopenia being a significant factor. Methods: The study enrolled 2369 participants aged ≥ 60 and collected demographic and anthropometric data.Various questionnaires, including the Short Form 12, Patient Health Questionnaire-9, Activities of Daily Living, and Instrumental Activities of Daily Living, were administered. Comparisons were made between individuals with and without osteosarcopenia. Regression models were employed to identify variables associated with HRQoL in those with osteosarcopenia. Results: Key findings revealed that 22.5% of participants had osteosarcopenia. Significantly different HR-QoL measures were observed between the 2 groups, especially in physical functioning and physical component summary scores. Male gender, advanced age, and chronic illnesses were linked to lower physical and mental HRQoL scores among those with osteosarcopenia. In female participants, a history of fractures and physical disability were associated with reduced quality of life. Conclusions This study underscores the negative impact of osteosarcopenia on HR-QoL, particularly in male participants, with a focus on physical aspects. It also highlights age and chronic disease as contributing factors to diminished HR-QoL in individuals with osteosarcopenia. These findings emphasize the importance of addressing osteosarcopenia in the elderly population to improve their overall well-being.