Purpose There is considerable inconsistency in results regarding the association of dietary glycemic index (GI) and glycemic load (GL) with cancer risk. We therefore conducted this systematic review and dose-response meta-analysis of prospective cohort studies to evaluate the relationship between dietary GI/GL and cancer risk. Methods We searched PubMed and Web of Science for prospective cohort studies of dietary GI/GL in relation to risks of all types of cancer up to 31 March 2021. We used a random-effect model to calculate summary relative risks (RR) and 95% confidence intervals (CI). The certainty of evidence was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. This study was registered at PROSPERO (CRD42020215338). Results Overall, 55 cohorts were included in the meta-analysis. We assessed the relationship between dietary GI or GL and risks of 23 cancer types, including hormone-related cancers, cancers from digestive system, respiratory system, urinary system and other cancer sites. High GI diet increased overall risk of cancer with low certainty of evidence (highest vs lowest categories, n = 3, RR 1.04, 95% CI 1.01-1.07). For site-specific cancers, high GI diet increased risks of lung cancer (highest vs lowest categories, n = 5, RR 1.08, 95% CI 1.01-1.18) and breast cancer (highest vs lowest categories, n = 14, RR 1.05, 95% CI 1.01-1.09), especially for postmenopausal breast cancer (highest vs lowest categories, n = 10, RR 1.06, 95% CI 1.00-1.13), all with low certainty of evidence. Additionally, dietary GI was positively related to risk of bladder cancer with low certainty of evidence (highest vs lowest categories, n = 3, RR 1.23, 95% CI 1.09-1.40), as well as negatively related to ovarian cancer risk with very low certainty of evidence (highest vs lowest categories, n = 4, RR 0.83, 95% CI 0.69-1.00) and lymphoma risk with low certainty of evidence (highest vs lowest categories, n = 2, RR 0.84, 95% CI 0.72-0.98). Besides, we found an inverse association of dietary GL with lung cancer risk with low certainty of evidence (highest vs lowest categories, n = 5, RR 0.87, 95% CI 0.80-0.94). Conclusion High dietary GI increased overall cancer risk with low certainty of evidence. For site-specific cancers, high GI diet increased the risks of breast cancer with low certainty of evidence and lung cancer with low certainty of evidence. Dietary GL was inversely associated with lung cancer risk with low certainty of evidence.