Considering the escalating resistance to conventional antifungal medications, it is critical to identify novel compounds that can efficiently counteract this challenge. The purpose of this research was to elucidate the fungicidal properties of secondary metabolites derived from Arcangelisia flava, with a specific focus on their efficacy against Candida species. This study utilized a combination approach comprising laboratory simulations and experiments to discern and evaluate the biologically active constituents present in the dichloromethane extract of A. flava. The in vitro experiments demonstrated that compounds 1 (palmatine) and 2 (fibraurin) exhibited antifungal properties. The compounds exhibited minimum inhibitory concentrations (MICs) ranging from 15.62 to 62.5 µg/mL against Candida sp. Moreover, compound 1 demonstrated a minimum fungicidal concentration (MFC) of 62.5 µg/mL against Candida glabrata and C. krusei. In contrast, compound 2 exhibited an MFC of 125 µg/mL against both Candida species. Based on a molecular docking study, it was shown that compounds 1 and 2 have a binding free energy of −6.6377 and −6.7075 kcal/mol, respectively, which indicates a strong affinity and specificity for fungal enzymatic targets. This study utilized pharmacophore modeling and Density Functional Theory (DFT) simulations to better understand the interaction dynamics and structural properties crucial for antifungal activity. The findings underscore the potential of secondary metabolites derived from A. flava to act as a foundation for creating novel and highly efficient antifungal treatments, specifically targeting fungal diseases resistant to existing treatment methods. Thus, the results regarding these compounds can provide references for the next stage in antifungal drug design. Further investigation is necessary to thoroughly evaluate these natural substances’ clinical feasibility and safety characteristics, which show great potential as antifungal agents.