Fungal infections represent a significant and growing global health burden, contributing to an estimated 1.5 million deaths annually, with the majority attributed to invasive mycoses caused by Candida, Aspergillus, and Cryptococcus species [1, 2]. The current therapeutic arsenal, comprising azoles, polyenes, and echinocandins, is increasingly compromised by the emergence of drug-resistant strains, dose-limiting toxicities, and narrow spectra of activity, particularly against uncommon but lethal pathogens [3, 4]. These limitations underscore the urgent need for novel antifungal agents capable of targeting resistant organisms through alternative mechanisms. Plant-derived phytochemicals, including flavonoids, alkaloids, terpenoids, and phenolic acids, have attracted considerable scientific interest as sources of new antifungal scaffolds with diverse mechanisms of action [5, 6]. Such compounds exert antifungal activity by disrupting fungal cell membrane integrity through ergosterol binding and depletion, inhibiting ergosterol biosynthetic enzymes, interfering with cell wall glucan synthesis, disrupting mitochondrial function, and dismantling fungal biofilms that confer resistance to conventional agents [7, 8]. Preclinical studies have demonstrated promising activity for numerous phytochemicals in both in vitro and animal models, though translational challenges including poor bioavailability, pharmacokinetic variability, and limited clinical data remain significant obstacles [9, 10]. Advanced formulation strategies, including nanoparticle encapsulation, lipid-based delivery systems, and nanotechnology platforms, offer potential solutions to enhance therapeutic efficacy. This review critically evaluates the current evidence for plant-based antifungal compounds, examines mechanistic frameworks, analyzes preclinical and clinical data, and discusses regulatory and commercialization challenges to inform future drug development strategies.