Monoterpenoids are well-recognized natural antimycotic agents, but their mechanism of action is still unclear. Interestingly, synthetic derivatives, as 4-bromothymol (4-bromo-2-isopropyl-5-methylphenol) are emerging as promising alternatives to natural molecules, due to their even greater biological activity. Herein, the antimycotic efficacy of 4-bromothymol was evaluated: in-vivo experiments on species of acclaimed resistance demonstrated that 4-bromothymol had a minimum inhibitory concentration (MIC) up to 6 times lower than thymol. In-silico investigations, sweeping from partition coefficient (LogP) determination, through density functional theory (DFT) and Molecular Dynamics (MD) simulations based on a Minimum Bias Approach (MBA), supported its improved anti-fungal activity with respect to thymol, carvacrol and thymyl acetate. A structural insight of the mechanism of action is proposed. Even though all the analysed compounds are able to penetrate the cellular membrane, 4-bromothymol shows a higher predicted affinity for the bilayer and it causes a strong perturbation at the water/bilayer interface, altering the stability of the membrane, thus leading to cell death.