The morphological transition of Candida spp. is a key virulence factor that enables these fungi to cause infections in humans. This ability to shift between yeast-like, hyphal, and pseudohyphal forms allows Candida species to adapt to diverse environments and hostile conditions, playing a critical role in pathogenicity. In this study, we investigated the effects of synthetic chalcones on the morphological transition of Candida albicans and Candida tropicalis, alongside an in silico evaluation of the compounds’ pharma- cokinetic properties, including absorption, distribution, metabolism, excretion, and toxicity (ADMET). To assess the inhibitory effects of chalcones and fluconazole on morphological transition, humid chambers were prepared and analyzed through optical microscopy. The predictions were performed using MarvinSketch (ChemAxon method), pkCSM, SMARTCyp, and Pred-Skin 3.0 platforms. The chalcones (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one (DB-Acetone), (1E,3E,6E,8E)-1,9-diphenylnona-1,3,6,8- tetraen-5-one (DB-CNM), and (1E,4E)-1,5-bis (4-methoxyphenyl)penta-1,4-dien-3-one (DB-Anisal), as well as fluconazole, com- pletely inhibited fungal morphological transition at the tested concentrations (MC, 1024 μg/mL, and MC/2, 512 μg/mL). In silico analyses revealed high intestinal absorption for all chalcones, with DB-Acetone and DB-Anisal showing potential for significant oral bioavailability. Moreover, all compounds demonstrated extensive tissue distribution and the ability to cross the blood-brain barrier. Despite some limitations, DB-Acetone, DB-CNM, and DB-Anisal were predicted to be well tolerated at high doses, with DB-Anisal emerging as the safest candidate based on toxicity profiles. Overall, these findings suggest that the synthetic chal- cones studied are promising agents for inhibiting the morphological transition of C. albicans and C. tropicalis, with DB-Anisal showing the most favorable pharmacokinetic and safety profile.