Carica papaya leaves are a popular remedy to treat Dengue-induced thrombocytopenia. There have been reports of Carica papaya effects as antibacterial, anti-parasitic, anti-cancer, and anti-inflammatory. There is limited evidence documenting the effects of Carica papaya on increasing platelet count in relation to Dengue infection. Moreover, the mechanism by which Carica papaya increases the platelet counts has not been elucidated. Understanding how Carica papaya affects platelet function may have implications beyond Dengue fever management. This study aims to investigate the mechanism by which Carica papaya affects platelet count. The mechanism of thrombocytopenia in the aqueous and methanol extracts was elucidated by measuring reactive oxygen species in platelets using chemiluminescence. Both aqueous and methanol extracts of Carica papaya leaves were found to increase reactive oxygen species levels in vitro. This study is the first to try to demonstrate the mechanism by which Carica papaya increases platelet count. Carica papaya leaves may be developed into novel and useful therapeutic agents in the management of thrombocytopenia-related disorders and cardiovascular diseases.