This study used a network pharmacology approach to investigate the potential active ingredients of Plantaginis Herba and its underlying mechanisms in hyperuricemia treatment. The potential active ingredients of Plantaginis Herba were obtained from TCMSP and ETCM databases, and the potential targets of the active ingredients were predicted using the Swiss TargetPrediction database. The potential therapeutic targets of hyperuricemia were retrieved from the GeneCards, DisGeNET, and Online Mendelian Inheritance in Man (OMIM) databases. Then, the integrative bioinformatics analyses of candidates were performed by GO analysis, KEGG analysis, and PPI network construction. There were 15 predicted active ingredients in Plantaginis Herba and 41 common targets that may be involved in the treatment of hyperuricemia. A total of 61 GO annotations and 35 signaling pathways were identified by enrichment analysis (P < 0.01). The underlying mechanisms of Plantaginis Herba may be related to insulin resistance, PI3K/AKT, TNF, VEGF, AMPK, and glucagon signaling pathways. Thus, the present study provided potential and promising strategies of Plantaginis Herba for hyperuricemia treatment. Copyright © 2021 Rong Tang et al.