The medicinal plant Vinca minor produces vincamine, a compound used for neurodegenerative diseases, along with a diverse array of monoterpenoid indole alkaloids (MIAs) primarily within the aspidosperma and akuammiline subclasses. While recent studies have elucidated the core biosynthetic pathways for these subclasses, the transformations of key intermediates into the vast diversity of naturally occurring alkaloids remain poorly understood. In this study, we identify and characterize two promiscuous cytochrome P450 monooxygenases (CYPs) in V. minor: vincaminoreine/pericyclivine 10-hydroxylase (VmV10H) and pseudoakuammigine 10-hydroxylase (VmPs10H), both exhibiting high substrate versatility. VmV10H catalyzes the hydroxylation of structurally diverse MIAs, including vincaminoreine, pericyclivine, apparicine, and akuammidine, while VmPs10H demonstrates a preference for akuammiline type MIAs such as pseudoakuammigine, picrinine, and strictamine. Homology modeling and substrate docking reveal active site architecture of these enzymes, suggesting a consistent mechanism for C10 hydroxylation across all substrates. The discovery of VmV10H and VmPs10H not only broadens our understanding of MIA biosynthesis but also expands the enzymatic toolkit for the metabolic engineering of pharmaceutical MIAs, including akuammine, a μ-opioid receptor agonist with analgesic properties.