5-Lipoxygenase (5-LOX) plays a key role in inflammation through the biosynthesis of leukotrienes and other lipid mediators. Current evidence suggests that dietary (poly)phenols exert a beneficial impact on human health through anti-inflammatory activities. Their mechanisms of action have mostly been associated with the modulation of pro-inflammatory cytokines (TNF-α, IL-1β), prostaglandins (PGE ), and the interaction with NF-κB and cyclooxygenase 2 (COX-2) pathways. Much less is known about the 5-lipoxygenase (5-LOX) pathway as a target of dietary (poly)phenols. This systematic review aimed to summarize how dietary (poly)phenols target the 5-LOX pathway in preclinical and human studies. The number of studies identified is low (5, 24, and 127 human, animal, and cellular studies, respectively) compared to the thousands of studies focusing on the COX-2 pathway. Some (poly)phenolics such as caffeic acid, hydroxytyrosol, resveratrol, curcumin, nordihydroguaiaretic acid (NDGA), and quercetin have been reported to reduce the formation of 5-LOX eicosanoids in vitro. However, the in vivo evidence is inconclusive because of the low number of studies and the difficulty of attributing effects to (poly)phenols. Therefore, increasing the number of studies targeting the 5-LOX pathway would largely expand our knowledge on the anti-inflammatory mechanisms of (poly)phenols.