Beh��et's disease (BD) is a multifaceted disorder of undetermined etiology. Distinct clinical manifestations exhibit varying prevalences, with mucocutaneous and ocular presentations being the most prevalent in the BD population. The aim of this study was to assess musculoskeletal (MSK) manifestations and their effect on health-related quality of life (HRQoL) of life in individuals with BD. We asked patients with BD to complete an online survey. The survey had many questions focused on demographic, clinical, and therapeutic data, as well as the Nordic musculoskeletal questionnaire and the short form-36 (SF-36). There was a total of 185 BD patients, mostly females (54.6%), with a mean age of 33.81 years. The most prevalent clinical manifestation was recurrent oral aphthosis (95.1%), followed by ocular involvement (72.4%). Most of the study patients (85.4%) reported MSK manifestations in the last 6 months. These manifestations included mainly the lower back (69%) and neck (67%), followed by the left and right knees (62% and 60%, respectively), while the least affected areas of the body were the right elbow (37%), and the right ankle and foot (7%). The age at disease onset (p���=���0.007) showed a statistically significant difference between those with MSK manifestations and those without. Patients exhibiting MSK manifestations demonstrated statistically significant lower scores of all SF-36 domains compared to those without such manifestations. MSK manifestations are prevalent and adversely affect HRQoL among BD patients. Therefore, early identification and treatment are strongly recommended.