The oral delivery of bile-based vesicles (BBVs) has been limited by their poor physical stability, low drug load and slow absorption rate. The novel consolidated bile-based vesicles/self-nanoemulsifying system (CBBVs/SNES) combines the advantages of vesicular and self-nanoemulsifying systems (SNES). This work aimed to prepare physically stable CBBVs/SNES loaded with the full dose of amlodipine besylate (AB) as model drug. AB-loaded BBVs dispersion was optimized using Box-Behnken design and evaluated for particle size distribution, encapsulation efficiency and solubilization efficiency. AB-loaded CBBVs/SNES was prepared by mixing the vesicles of the optimized BBV with Labrafil-based SNES that gave the highest drug solubility. AB-loaded CBBVs/SNES was evaluated for particle size, Polydispersity index (PDI) and in vitro release. When diluted in GIT fluids, consolidated system spontaneously emulsifies forming nanosized oil droplets and in-situ formed mixed micelles. The formation of nanosized mixed micelles (<100 nm) was confirmed by transmission electron microscopy and particle size analysis (PS; 106.8 ± 17.60 nm and PDI; 0.20 ± 0.01). The developed CBBVs/SNES showed enhanced physical stability when stored for 3 months at 2–8 °C. The ex-vivo transport study confirmed that the developed CBBVs/SNES improved the drug transport about 3.8 folds in comparison to the reconstituted vesicular dispersion through offering three pathways of transport (in-situ formed mixed micelles uptake, nanoemulsion droplet uptake and vesicular uptake). The various offered transport pathways and the improvement of drug load and physical stability propose that CBBVs/SNES administered via the oral route could therefore be promising in oral delivery of vesicular systems. In-vivo studies is presently investigated.