Rationale Orientin and isoorientin are C‐glycosidic flavonoids, considered as markers of some plant species such as Passiflora edulis var. flavicarpa Degener, and reported in the literature to have pharmacological properties. In order to evaluate and characterize the in vitro metabolism of these flavonoids, phase I biotransformation reactions were simulated using Salen complexes. Methods These flavonoids were oxidized separately in biomimetic reactions in different proportions, using one oxidant, m‐chloroperbenzoic acid or iodosylbenzene, and one catalyst, the Jacobsen catalyst or [Mn(3‐MeOSalen)Cl]. The [Mn(3‐MeOSalen)Cl] catalyst was synthesized and characterized using spectrometric techniques. The oxidation potentials of the catalysts were compared. All reactions were monitored and analyzed using ultrahigh‐performance liquid chromatography diode‐array detection (UHPLC‐DAD) and high‐performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). Results The analysis by UHPLC‐DAD and HPLC/MS/MS showed that isoorientin produces more products than orientin and that [Mn(3‐MeOSalen)Cl] produces more products than the Jacobsen catalyst. In addition, [Mn(3‐MeOSalen)Cl], which has a higher oxidation potential, formed products with the addition of one or two atoms of oxygen, while the Jacobsen catalyst formed compounds with only one added oxygen atom. The products with the addition of one oxygen atom were mainly epoxides, while those with two added oxygens formed an epoxide in the C‐ring and incorporated the other oxygen into the glycosidic moiety. Conclusions The formation of epoxides is common in biomimetic reactions and they may represent a safety risk in medicinal products due to their high reactivity. This study may serve as a basis for subsequent pharmacological and toxicological studies that investigate the presence of these compounds as phase I metabolites, and ensure the safe use of plant products containing orientin as a chemical marker.