Background: The significant role of red blood cell distribution width (RDW) and D-Dimer as prognostic factors in patients with some blood malignancies has been reported recently. Aim: We designed and performed a meta-analysis to investigate the prognostic roles of RDW and D-Dimer in subjects with diffuse large B-cell lymphoma (DLBCL). Materials and Methods: We systematically reviewed PubMed-Medline, SCOPUS, EMBASE, Web of Science Core Collection, and Google Scholar up to 30 April 2023 to look for publications on prognostic effects of RDW and D-Dimer in DLBCL patients. For investigation of the associations between RDW and D-Dimer with the overall survival (OS) and progression-free survival (PFS) of the DLBCL cases, hazard ratio (HR) with 95% confidence intervals (CIs) was used. Results: We included 13 eligible studies in the present meta-analysis. The results of pooled analysis showed that increased levels of RDW was related to poor OS (HR=2.01, 95% CI: 1.62-2.48, P value<0.01) and poor PFS (HR=1.52, 95% CI: 1.24-1.85, P value<0.01) among the DLBCL patients. On the other hand, a significant relationship was found between increased D-Dimer and poor OS (HR=2.30, 95% CI: 1.03-5.14, P value<0.05) of the DLBCL patients as well. Conclusion: Our finding clearly confirmed that elevated RDW levels and D-Dimer were associated with adverse OS and PFS in DLBCL.