Purpose <p>This prospective study is aimed at assessing the effect of aerobic exercise on adipokine and myokine biomarkers of breast or colon cancer patients during chemotherapy.</p> Methods <p>Thirty-two patients (15 exercise, 17 control) were included in this study. In total, 27 out of 32 and 26 out of 32 patients were female and diagnosed with breast cancer, respectively. The exercise protocol was performed via stationary resistive cycle ergometer during chemotherapy 2 times each week for at least 12&#xa0;weeks. Circulating serum biomarkers of IL-6, irisin, leptin, and adiponectin levels were measured before chemotherapy and after the last chemotherapy cycle. The intensity of exercise was set as submaximal (50–70% of heart rate reserve (HRR)). Each patient was started with the intensity of exercise at the rate of 50% of their maximal HR. Each supervised exercise session lasted for 35&#xa0;min.</p> Results <p>The mean exercise duration (weeks) and percent adherence rates in the EG were 19.20 ± 3.63&#xa0;weeks and 85.13 ± 11.87, respectively. In EG, there were significant increases in IL-6 (<i>t</i> = − 2.985, <i>p</i> = 0.011) and adiponectin (<i>z</i> = − 2.229, <i>p</i> = 0.026). Although a nearly 10% increase was observed in Irisin levels (0.83 vs. 0.91), it did not reach statistical significance (<i>t</i> = 0.840, <i>p</i> = 0.416). In EG, the correlation between Δ of leptin and adiponectin (<i>r</i> = − 0.635, <i>p</i> = 0.015) and the correlation between Δ of leptin and irisin (<i>r</i> = 0.802, <i>p</i> = 0.001) were found significant. No significant change was observed in each biomarker for CG.</p> Conclusion <p>This study demonstrated that aerobic exercise can be safely implementable and beneficial during chemotherapy with significant effects on anti-inflammatory biomarkers via increased levels of IL-6 and adiponectin.</p> <p><b>Trial registration.</b></p> <p>NCT07048847, date of registration: 02.07.2025, “retrospectively registered”.</p>