The two-dimensional (2D) and three-dimensional (3D) structures of bioactive compounds from Catharanthus, such as vincristine, vinblastine, and ajmalicine, provide crucial insights into their pharmacological actions. These structures reveal functional groups, stereochemistry, and molecular conformations essential for biological activity. The key physicochemical properties include molecular weight, lipophilicity (log P), hydrogen bond donors/acceptors, and topological polar surface area (TPSA), which influence solubility, permeability, and drug-likeness. 3D modeling aids in understanding target binding interactions and optimizing drug design. Structure–activity relationship (SAR) and quantitative structure–activity relationship (QSAR) studies further highlight the role of spatial orientation and electronic distribution in modulating therapeutic efficacy and bioavailability of Catharanthus-derived compounds.