Chinese practitioners have employed the use of traditional Chinese medicine as an anti-cancer agent since the ancient period. Different combinations have been formulated for various purposes. Some have been claimed for post-chemotherapy use but their direct actions on cancer cells may not be significantly reported. In the present study, we have tested the possible anti-leukemia potential of a combination regimen including crocodile egg extract, wild radix ginseng and natural Ganoderma lucidum (CGG extract) on acute myelogenous leukemia (AML) in vitro. A water soluble CGG extract was prepared and its antiproliferative activity was tested on the KG1a AML cell line and two freshly prepared bone marrow aspirate samples isolated from patients with de novo AML during presentation by a MTS/PMS assay. Furthermore, the possible activity of the CGG extract on the regeneration potential of KG1a cells was also investigated using a semi-solid methyl-cellulose colony formation assay. Lastly, the acute toxicity of CGG extract was further examined by a single high-dose oral feeding to rats. We found that the CGG extract could possess significant antiproliferative activity on AML cells. A strong colony formation inhibition was further demonstrated on KG1a cells. After feeding the rats with an excessive dose of CGG extract, we observed no development of acute toxicity. We concluded that the CGG extract has growth inhibitory potential on KG1a cells and AML bone marrow samples in vitro. An in vivo toxicity test revealed that no acute toxicity was observed after feeding the rats a high dosage of the CGG extract. Further animal model tests are necessary to investigate the possible chronic toxicity of the CGG extract.