We evaluated the effect of exercise therapy on back pain, spinal range of motion (ROM), and disability in persons with diffuse idiopathic skeletal hyperostosis (DISH). Persons with symptomatic DISH received a daily exercise program for 24 weeks consisting of mobility, stretching, and strengthening exercises for the cervical, thoracic, and lumbar spine. It included 14 supervised sessions over 8 weeks. Outcomes included visual analogue scales (VAS) for pain, stiffness, and fatigue, 13 spinal measurements, the neck pain and disability scale, the Quebec back pain disability scale, the Bath Spondylitis Functional Index, and the MACTAR patient preference scale. Assessments were made at baseline, 8 weeks, and 24 weeks. Fifteen of 17 completed the study. Comparing week 24 with baseline, Schober’s test improved significantly (p = 0.02), and VAS stiffness and left finger-to-floor test demonstrated a trend to improvement (p = 0.07 each). The physical measures, which were expected to improve with the exercise program, all moved in the direction expected, but had p values > 0.10. At 24 weeks, eight (53.3%) participants rated their status as improved, three (20%) as unchanged, and four (27%) were unsure about the benefit. The exercise program designed for DISH and tested in this study led to small improvements in physical measures which achieved significance only for lumbosacral flexion.