Purpose <p>While some studies have investigated the effectiveness of exercise interventions during adjuvant chemotherapy in cancer patients, the findings are inconclusive. This systematic review and meta-analysis aimed to quantify the effectiveness of exercise interventions specifically in patients with colorectal cancer (CRC) during adjuvant chemotherapy.</p> Methods <p>A comprehensive literature search was conducted using 6 electronic databases. Eligible studies included randomized controlled trials (RCTs), non-RCTs, single-arm intervention studies, and retrospective cohort studies that implemented structured exercise interventions. Exercise capacity, lower and upper extremity muscle strength, fatigue, pain, chemotherapy-induced peripheral neuropathy, anxiety, depression, and quality of life were defined as outcomes. A meta-analysis was performed to quantify the effectiveness of exercise interventions during adjuvant chemotherapy on each outcome. Additionally, the feasibility of the exercise interventions was investigated.</p> Results <p>Nine studies met the inclusion criteria for the present systematic review. In the RCTs, exercise interventions during adjuvant chemotherapy significantly reduced fatigue (standardized mean difference [SMD]: -0.53 [95% confidence interval {CI}: -1.04, -0.01]) and depression (SMD: -0.34 [95% CI: -0.55, -0.13]), but had no significant effect on exercise capacity, lower and upper extremity muscle strength, pain, anxiety, and quality of life. Adherence to exercise interventions during adjuvant chemotherapy ranged from 58 to 100%. No adverse events were reported, or reporting was not provided.</p> Conclusions <p>This systematic review revealed that exercise interventions during adjuvant chemotherapy effectively reduce fatigue and depression in patients with CRC, though the effect may be small. The implementation of exercise interventions during adjuvant chemotherapy may be safe.</p>