Rates of Erectile Dysfunction (ED) continue to rise each year. Synthetic pharmacological agents used for ED frequently produce unwanted reactions, and their therapeutic performance is limited. Within Indonesia, several native plants have traditionally been used to manage ED symptoms. This review seeks to compile updated scientific data on Indonesian medicinal plants with potential efficacy against ED and to clarify their molecular actions using a systematic review and a Pharmacological Network framework. A total of 12 candidate plant species widely employed by Indonesian ethnic groups for treating ED were identified. Literature searches were performed in PubMed, Scopus, and Springer without restricting publication date. Article selection followed the PRISMA workflow. Compound-related gene targets were identified via GeneCards, while disease-associated genes were obtained from DisGeNET. Network features were analyzed using Cytoscape 3.10, and STRING 12.0 supported the creation of Protein–Protein Interaction maps. Subsequent GO and KEGG enrichment analyses were completed using SRplot. The systematic review ultimately included 12 publications matching the eligibility standards. Pharmacology Network evaluation showed that constituents of Eurycoma longifolia—particularly stigmasterol, eurycomanone, and eurycomalactone—interact with 13 ED-related genes: BCL2, AKT1, SOAT1, PCSK9, ACHE, BDNF-AS, TMX2-CTNND1, GSK3B, LINCO1672, TP53, H19, HIF1A, and IL1B. These genes participate in pathways linked to steroid hormone biosynthesis, a key process in testosterone formation. Thus, Eurycoma longifolia emerges as a strong phytopharmaceutical candidate for improving sexual function.
