Gourami fish is a popular and economical fishery culture commodity in Indonesia. One of the bacterial diseases that is an obstacle in gourami fish culture is Edwardsiellosis, caused by the Edwardsiella tarda bacteria. The aim of this study was to examine the viability of croton leaf (Codiaeum variegatum) as a natural substitute for synthetic antibacterial in addressing E. tarda infection. This study used a two-phase approach, identification of antibacterial compounds from C. variegatum leaves and their effectiveness against E. tarda. The treatments were negative control (K-), positive control (K+), C. variegatum with doses of 500, 550, 600, 650, and 700mg/ L (seven treatments and three replication). The results indicated that C. variegatum primarily comprised antibacterial compounds of flavonoids, alkaloids, tannins, and terpenoids. The utilization of the raw extract from C. variegatum significantly influenced the infected gourami fish's hematology. It was found that 600mg/ L was the most efficient dose to overcome E. tarda infection in gourami fish, leading to significant improvements hematological parameter. Moreover, histopathological examination indicated enhancements in tissue profile, as evidence by lower congestion, necrosis, and degeneration score. Additionally, after being treated with 600mg/ L dose of C. variegatum extract, the gourami fish's survival rate reached 83%. These findings underscore the potential efficacy of C. variegatum as a promising treatment for managing gourami fish infection caused by E. tarda. Nonetheless, further investigation is warranted to evaluate the practical application of C. variegatum in gourami fish aquaculture.