Irisin seems to play an important role in several chronic diseases, however, the interactions between chronic training and irisin are still unclear. The purpose of this systematic review and meta-analysis was to examine the effect of chronic resistance training on circulating irisin in adults. Literature search was conducted in PubMed, Web of Science and EBSCOhost (Academic Search Complete) until December 2020. Randomized controlled trials researching irisin levels after a resistance training program for at least 8 weeks among an adult population were eligible. Other inclusion criteria comprised recruiting a control group and reporting circulating irisin through ELISA kits. Cohen’s d effect size and subgroup analyses (95% confidence level) were calculated using a random effects analysis model. Data of the seven included studies comprising 282 individuals showed an increasing and non-significant tendency after a resistance training program (d = 0.58, 95% CI: −0.25 to 1.40, p = 0.17). Subgroup analyses showed significant increases for the older adults group (p < 0.001) and when training is demanding and progressive in terms of intensity (p = 0.03). Data suggest that resistance training programs seem to increase circulating irisin, especially in older adults and in demanding and progressive training programs. However, more studies should be conducted using robust measurement methods, such as mass spectrometry, to better understand the interaction between chronic resistance exercise and irisin.