Chronic hepatitis B, primarily caused by the Hepatitis B virus, is prevalent in Korea and significantly contributes to liver cancer. Tenofovir disoproxil fumarate (TDF), a key treatment for hepatitis B, is preferred for its efficacy and low resistance. Recently, potential positive side effects, such as weight loss and lipid-lowering, have been contentious, especially since weight gain and high lipid levels are known to influence liver cancer. This study aimed to assess the association between TDF use and adverse events of weight loss and lipid-lowering in chronic hepatitis B patients using data from the Korean Adverse Event Reporting System (KAERS) and the US FDA Adverse Event Reporting System (FAERS) from 2013 to 2022. Disproportionality analysis was conducted on patients reporting adverse events after nucleotide analogues. Despite examining 6,688 reports (11,245 drug-adverse event pairs) from KAERS and 35,656 reports (126,060 drug-adverse event pairs) from FAERS, no significant weight loss or lipid-lowering signals were found. The findings suggest TDF may not be linked to these adverse events, though ongoing monitoring and cautious interpretation are advised, as the study does not establish causality.