Ironized multivitamin-loaded liposomes were generated via the use of supercritical-CO2 (SC-CO2) as a green solvent without using any organic solvent. A newly developed, venturi-based rapid expansion of a supercritical solution (Vent-RESS) system was employed to introduce lipophilic and hydrophilic bioactives in an eductor vacuum system and efficiently mix them together in a fraction of a second without the aid of an external pump to generate liposomes. Firstly, two different coating materials, lecithin with 39% and 13% of phosphatidylcholine (PC), were used to study the structure of the resulting liposomes and the zeta-potential of the colloidal system. Then, lecithin with 13% of PC was selected for the microencapsulation purpose due to its better interaction with other hydrophobic components incorporated into the lamellar part of the liposomes. The lipophilic part included lecithin, cholesterol, and a lipophilic cargo, vitamin E; whereas the hydrophilic phase consisted of iron sulfate and vitamin C solution. It was found that liposomes of a unimodal size distribution with an average size range of 580–700 nm were formed when the SC-CO2 pressure was changed from 12 to 18 MPa. Additionally, the encapsulation efficiency of vitamins C and E and iron sulfate was improved to the maximum values of 60%, 88%, and 58% from 46%, 36%, and 12%, respectively, when the pressure was increased from 12 to 18 MPa. The finite volume method (FVM) was used to numerically simulate the mixing of the two fluid streams to better understand the effect of the hydrophilic cargo introduction geometry on the mixing efficiency. This microencapsulation system is based on a green approach to generate hydrophilic/lipophilic bioactive-loaded liposomes, free of organic solvents with high potential for scale-up, which can be used in food, biomedical, and cosmetic applications.