Background There are no clear conclusions as to whether inflammatory proteins and plasma metabolites influence erectile dysfunction (ED).Aim In this research, we used Mendelian randomization (MR) analysis to discover a causal relationship between inflammatory proteins, plasma metabolites, and ED.Methods Raw data with ED, inflammatory proteins, and plasma metabolites were obtained from the MRC IEU OpenGWAS and FinnGen database. After a series of screenings, the remaining single nucleotide polymorphisms were selected as instrumental variables or MR analysis to assess the relationship between genetically predicted inflammatory proteins or plasma metabolites and the pathogenesis of ED.Outcomes The relationship between inflammatory factors and ED was fully analyzed and elaborated.Results In the inverse variance-weighted method, there exists a significant causal relationship between 4 types of genetically predicted inflammatory proteins and 50 types of plasma metabolites with the incidence of ED. The primary discovery is that 3 inflammatory proteins, fibroblast growth factor 5, interleukin-22 receptor subunit alpha-1, and protein S100-A12, can impact the risk of ED through plasma metabolites.Clinical Implications ED metabolites and inflammatory proteins are also closely associated with cardiovascular diseases, warranting further exploration.Strengths and Limitations Our analysis is based on a European population, limiting its generalizability, the genome-wide association study dataset for ED has a relatively small number of cases, and we hope for larger genome-wide association study datasets for future validation.Conclusion This study has identified that inflammatory proteins can influence ED through plasma metabolites.