Abstract: Objective: The mechanism of action of Nelumbo nucifera leaf alkaloids in the treatment of hyperuricemia was analyzed based on network pharmacology and molecular docking. Methods: The target of Nelumbo nucifera leaf alkaloids and disease targets related to hyperuricemia were obtained through database search. The "component-disease-target" network of Nelumbo nucifera leaf alkaloids was established through Cytoscape 3.8.0, and the gene ontology (GO) analysis and Kyoto encyclopedia of genes and genome (KEGG) pathway analysis were carried out using the bioinformatics-based platform. The core target and key components were verified by molecular docking. Results: The information of 27 kinds of Nelumbo nucifera leaf alkaloids, including nuciferine, coclaurine, liensinine, was obtained by literature search, and 337 corresponding targets, 926 hyperuricemia-related targets and 57 key targets were piedicted. The mechanism of action of Nelumbo nucifera leaf alkaloids in the treatment of hyperuricemia mainly involved GAPDH, STAT3, JUN, CASP3, PTGS2, XDH, MAPK1 and other target genes. These genes mainly played a role in regulating protein expression through AGE-RAGE signaling pathway, PD-L1 expression and PD-1 checkpoint pathway, TNF signaling pathway, IL-17 signaling pathway and p53 signaling pathway. The results of molecular docking showed that the compound had good docking results with the molecular target. Nuciferine, coclaurine and liensinine bound to the key targets spontaneously, among which liensinine formed the most stable structure with PTGS2 and JUN, and the binding energy could reach −9.3 kcal/mol. Conclusion: This study predicted that Nelumbo nucifera leaf alkaloids could ameliorate hyperuricemia by regulating multiple targets and action multiple pathways, which could provide scientific basis for molecular research of Nelumbo nucifera leaf alkaloids in the treatment of hyperuricemia.