This article reports on a new way of valorizing vine leaves waste as a renewable resource of polyphenols. The nanoparticles containing zinc complexes were prepared by a green synthesis method using the aqueous extract of vine leaves as a natural source of ligands for the complexation of zinc ions. The prepared nanoparticles were characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) in conjunction with energy dispersive X-ray spectroscopy (EDX). Another objective of this study was to obtain a cream into which the biosynthesized nanoparticles would be incorporated. In the formulation of the new cream, we aimed to use the minimal required amounts of synthetic emulsifiers and to use natural products as co-emulsifiers or as viscosity modifiers. The organoleptic characteristics and the physicochemical properties of the obtained creams were evaluated. The experimental results confirmed that the creams wherein the nanoparticles containing zinc complexes were incorporated exhibited antimicrobial activity against the bacterial species Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Escherichia coli and the yeast Candida albicans. The values obtained for pH, viscosity and spreading diameter of the creams produced indicate that these formulations are suitable for topical applications.