Background It was aimed to investigate the musculoskeletal status in individuals diagnosed with skeletal discrepancies. Methods This case–control study was performed on 35 patients with developmental skeletal discrepancies listed for orthognathic surgery as a case group and 33 patients who were nominated for wisdom tooth removal as a control group. All participants were aged 18–40 years and the research was carried out in the period between May 2018 and May 2019. Dual X-ray absorptiometry (DEXA) was used to assess bone mass density at three bone sites: total hip, femoral neck, and the spinal lumbar vertebrae (L1-L4). The appendicular muscle mass index (ASMI) was measured based on the four limbs from the DEXA scan. Results Our data showed that 45.7% (16) of the case group were osteopenic or osteoporotic while in the control group only 21.2% (7) were osteopenic in at least one region (total hip, femoral neck, or lumbar) (p-value = 0.03). Regarding muscle mass, there was significantly lower SMI in subjects with skeletal discrepancies (case group) compared with the control group (median (IQR) 5.9 (2.5) vs. 6.8 (2.9) (kg/m2), respectively, p = 0.04). Conclusions There is an essential need for more studies to understand the exact interrelationship between musculoskeletal status and skeletal jaw discrepancies.