Abstract Context Patients with colorectal cancer have increased risk of metabolic diseases including diabetes. Exercise training may counteract metabolic dysregulation, but the impact of exercise training on glycemic control, including postprandial glycemia, has never been explored in patients with colorectal cancer. Objective To examine the effects of home-based interval walking on aerobic and metabolic fitness and quality of life in patients with colorectal cancer. Design Randomized controlled trial. Setting Clinical research center. Participants Thirty-nine sedentary (<150 minutes moderate-intensity exercise per week) patients with stage I to III colorectal cancer who had completed primary treatment. Intervention Home-based interval walking 150 min/wk or usual care for 12 weeks. Main Outcome Measures Changes from baseline to week 12 in maximum oxygen uptake (VO2peak) by cardiopulmonary exercise test, glycemic control by oral glucose tolerance test (OGTT), body composition by dual-energy x-ray absorptiometry scan, blood biochemistry, and quality of life. Results Compared with control, interval walking had no effect on VO2peak [mean between-group difference: −0.32 mL O2 · kg−1 · min−1 (−2.09 to 1.45); P = 0.721] but significantly improved postprandial glycemic control with lower glucose OGTT area under the curve [−126 mM · min (−219 to −33); P = 0.009], 2-hour glucose concentration [−1.1 mM (−2.2 to 0.0); P = 0.056], and improved Matsuda index [1.94 (0.34; 3.54); P = 0.01]. Also, interval walking counteracted an increase in fat mass in the control group [−1.47 kg (−2.74 to −0.19); P = 0.025]. Conclusion A home-based interval-walking program led to substantial improvements in postprandial glycemic control and counteracted fat gain in posttreatment patients with colorectal cancer, possibly providing an effective strategy for prevention of secondary metabolic diseases.