Supramolecular complex based on Gemini amphiphilic pseudopeptides (GAP 5a) and para coumaric acid (p-CA) was designed, synthesized and formulated into nanovesicles as drug delivery system for brain cancer therapy. Molecular docking and molecular dynamics simulations revealed strong GAP 5a/p-CA interactions and favorable translocation across lipid bilayers. GAP 5a/p-CA nanovesicles exhibited spherical morphology, a negative surface charge and an average particle size of 306.5 nm, enabling efficient tumor targeting. Notably, GAP 5a nanovesicles achieved high drug entrapment efficiency (90.7 %) and pH-responsive release, with faster drug liberation under acidic conditions mimicking the tumor microenvironment. Additionally, in vitro release studies demonstrated a more controlled release of the drug from nanovesicles compared to drug solution. Loading p-CA on GAP 5a nanovesicles resulted in a two-fold increase in the drug's cytotoxicity on Glioma GL261 cancer cells, from IC50 936 μg/mL to 451 μg/mL, consistent with formulation-dependent effects playing a key role. p-CA and GAP 5a scored high IC50 values on VERO cells implying good safety profile of the prepared novel system. Nonetheless, the in-vitro IC₅₀ values lie in the high μg/mL range, limiting immediate translational prospects. Accordingly, these findings pave the way for further optimization of GAP nanovesicles as promising carriers of polyphenol model p-CA towards brain cancer cells.