Abstract Whole-body cryotherapy (WBC) is increasingly being studied and used in various populations, mainly focusing on improving the body’s regenerative capacity. More comprehensive summaries of anti-inflammatory responses are needed. To systemically assess the effect of WBC on the inflammatory response in humans based on randomized controlled trials (RCTs). Articles about RCTs accessing the effects of whole-body cryotherapy on the levels of inflammatory factors in humans published until August 1, 2024 had been searched in PubMed, Web of Science, Embase and Cochrane library databases. The general information of the included articles and exposure mode, the types and levels of inflammatory factors in serum were extracted. The PEDro scale was used to assess the risk of bias, and the GRADE scale was used to assess the level of certainty of evidence. RevMan 5.4 software were used to conduct the meta-analysis. A total of 11 RCTs in 11 articles were included, and the total sample size was 274. The level of IL-1β in serum of people exposed to WBC was lower than that in control group (SMD value was − 2.08pg/mL, P