Eucalyptus (Eucalyptus globulus Labill.) is an evergreen tree found worldwide. The aqueous ethanolic extract of the leaves (eucalyptus leaf extract; ELE) is used as a functional food, and its active constituents are generally polyphenols. Toxicity and mutagenicity of ELE have been previously assessed using rodents, and no adverse effects were observed. Although clinical trials of low-dose ELE ingestion have been conducted on humans, safety evaluation of high-dose ELE has not yet been conducted. We conducted an open-label clinical trial as a pilot study to assess the safety of excessive oral intake of ELE in Japanese adult men. A powdery preparation of ELE, commercially sold as Eucagrandin®, was prepared using spray drying method and contained approximately 80% ELE. Test capsules were packed with the powdery ELE. Six male subjects (aged 47.3 ± 12.4 years, mean ± SD) orally consumed 2,592 mg of ELE per day for 4 consecutive weeks. The subjects were examined at the start of the intervention, 4 weeks after the start, and 2 weeks after the last intake of test capsules. During the study period, 2 adverse events were reported. However, the causal relationship with the consumption of ELE was denied in both events because one event was attributed to a bruise and the other, which was elevated CPK levels, was due to excessive exercise. No unusual changes related to ELE consumption were observed in physical examination and during medical interviews. Further, blood and urine tests were normal during the trial period. These results demonstrated that oral consumption of ELE at the indicated dose is safe for humans.