Recent interventional investigations suggest the beneficial impact of propolis supplementation on inflammatory biomarkers; however, the results have not been summarized in a comprehensive meta-analysis. We conducted this meta-analysis to summarize all available data and provide clear evidence for whether propolis supplementation affects inflammatory biomarkers. This systematic review with meta-analysis was performed by searching databases (PubMed/Medline, Web of Science, Scopus, and Embase) until February 2024. It included randomized clinical trials (RCTs) assessing the effects of propolis supplementation on inflammatory biomarkers in adults. This review included 20 RCTs with a total of 1139 participants. The propolis supplementation significantly reduced IL-6 (WMD = -2.48; 95 % CI: -4.62, -0.34; P = 0.023) and TNF-α (WMD = -0.86; 95 % CI: -1.45, -0.26; P = 0.005) compared with control groups. Although the CRP concentration was not reduced (WMD = 0.01; 95 % CI: -0.03, 0.05, P = 0.646), a significant reduction in CRP levels was revealed in supplementation durations ≥ 10 weeks. These results suggest that propolis has a beneficial effect on TNF-α and IL-6 levels and may be an effective adjunctive therapy for diseases where inflammation is a key factor in the etiology. Due to the limited number of studies, clinical diversity, and other limitations, it is necessary to conduct more high-quality studies to provide more precise and comprehensive recommendations.