Objective: Based on the discovery and summary of adverse drug reactions of nucleotide analogues against herpes virus drugs, this study aims to analyze the situations of ADRs in the real world, put forward reasonable drug use recommendations, refine the rules of use, and formulate necessary alternative strategies to provide protection against herpes virus infection, and provide guidance and reference for the rational and individualized use of clinical drugs. Methods: All ADRs data of the drugs from the Q1 of 2004 to the Q4 of 2022 were obtained from the FDA Adverse Event Reporting System database. Duplicate reports, reports with uncertain information, and other reports containing abnormal information were excluded from the obtained data, and the data with more than 3 reports were selected. Apply the ROR, PRR and BCPNN in the disproportionality analysis for data mining . Results: All data from the Q1 of 2004 to the Q4 of 2022 were screened from the FAERS database. For ADEs with high frequency SOC level, we found that several important signals, including ADEs of ACV, GCV and VACV, simultaneously involved the following SOC systems: kidney and urinary system diseases, nervous system disease, skin and subcutaneous tissue diseases and mental diseases. Conclusion: Analysis of the FAERS database suggests that in addition to paying attention to efficacy, drug administration should be individualized according to the specific condition and potential risk of disease.