The use of conventional drugs in treating inflammation has various side effects, and thus it is necessary to have an alternative anti-inflammatory agent that is effective and safe. Cocoa (Theobroma cacao L.) is one of the agricultural products with a high content of polyphenols, especially flavan-3-ols potentially used as an anti-inflammatory agent. The purpose of this research is to investigate the research gap of the potential antiinflammatory activity of cocoa based on the published literatures. The systematic method of synthesizing the review follows the guidelines of the PRISMA Statement 2020 using the PICOS literature search strategy. The results of this study showed that the positive effect of cocoa on inflammation indicated by 44 out of 72 biomarkers (61.11%). Flavan-3- ols can effectively reduce inflammation by reducing the activation of transcripts that regulate pro-inflammatory cytokines (NF-kB), prostaglandins, and NO. The antiinflammatory effect was effectively found in different groups, i.e., subjects without health issue (healthy subject), subjects with some health problems record and subjects with obesity. Nevertheless, it was found in the previous researches that the manifest of cocoaderived products as well as the biomarkers for determining the anti-inflammatory effect of cocoa still vary. Also, there is no study investigating the anti-inflammatory effect of cocoa on different age group. Therefore, further researches are required in this area to complete the puzzle of information regarding the potential anti-inflammatory activity of cocoa.