Background: Candida krusei is the cause of the fungal infection candidiasis, which has a high mortality rate. Intrinsic resistance to fluconazole can cause the failure of Krusei candidiasis treatment. Therefore, it is necessary to find alternative drugs to eliminate the fungus. Extracts of Syzygium aromaticum and Alpinia purpurata have been proven to be alternative solutions for treating Candida krusei resistance. Objective: This study aims to explore the active compounds Syzygium aromaticum and Alpinia purpurata as treatments against Candida krusei through bioactivity tests, molecular modeling, and toxicity tests. Methods: Determination of antifungal activity with the agar well diffusion and microbroth dilution method. Molecular modeling was conducted using the following software: Marvin Sketch, LigandScout 4.4.5, AutoDock ver 4.2.6, PyMOL, LigPlus, MOE ver 2008. Result: Bioactivity test results of the two natural extracts against C. krusei ATCC 6258, it was found that the S. aromaticum and A. purpurata extracts have MIC50 values of 0.031 μg/mL and 1.435x105 μg/mL. The molecular modeling found that the compounds Benzotriazole, 1-(4-methyl-3-nitrobenzoyl)-, 1,3,4-Eugenol Acetate, Stigmasta-5,22-dien-3-ol, acetate (3 beta)- and Farnesyl acetate from the two natural extracts, interacts with the active site of the enzyme lanosterol-14-α-demethylase with a binding energy of -8.91, -6.04, -13.53, and -7.15 kcal/mol. The oral acute toxicity test of S. aromaticum and A. purpurata extracts proved that the LD50 was?>6000 mg/kg BW and?>8000 mg/kg BW. The acute dermal toxicity test of the two extracts showed that the LD50 was?>6000 mg/kg BW. Conclusion: S. aromaticum and A. purpurata extracts have been proven to be alternative solutions for treating Candida krusei resistance. © This work is licensed under a Creative Commons Attribution-Non Commercial 4.0 International Li