Muscle pull from regular physical activity is crucial for optimal development of the skeleton during growth and maintenance of bone mineral density (BMD) throughout life. Mitochondrial Respiratory Chain Disorders (MRCD) and Cystic Fibrosis (CF) are two chronic diseases that exhibit reduced lean tissue mass and impaired exercise capacity, which negatively impacts bone health in these populations. Whole body vibration training (WBVT) is an emerging therapeutic modality that has been successful in improving BMD and muscle mass and function in heath and disease. Aim: To evaluate whether 6 months of home-based WBVT improves BMD, muscle function, exercise capacity and quality of life (QoL) in people with MRCD or CF. Methods: Participants were enrolled for 15-18 months: 3-6 months observation; 6 months home-based WBVT (3 x 3mins daily at 20Hz on a Galileo® Home vibration platform); 6 months follow-up. Participants attended four study visits and completed: dual energy x-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) to assess BMD; muscle function testing on the Leonardo Jumping Platform (LJP); 6-minute walk test (6MWT) and/or formal exercise testing to assess exercise capacity; and disease specific QoL questionnaires. Linear mixed models analysis was used to assess changes between visits. Results: The MRCD cohort had 23 participants (13 male) mean (SD) age 31.0 (19.8) years and the CF cohort, 16 participants (8 male) mean (SD) age 12.8 (3.5) years. Statistically significant improvements in BMD of the legs were seen in the MRCD and CF cohorts for both DXA and pQCT. Muscle force during hopping and co-ordination during the chair rise test on the LJP improved significantly post WBVT in the CF. Exercise capacity did not change in the MRCD or CF cohorts after WBVT. QoL showed improvements in both cohorts. Conclusions: WBVT was well tolerated. WBVT improved BMD, aspects of muscle function, and QoL in people with MRCD or CF and may be a useful adjunct to physiotherapy exercise programs.