Polyamidoamine hydrogels prepared by the radical post-polymerization of α,ω-bisacrylamide-terminated M-AGM oligomers, in turn obtained by the polyaddition of 4-aminobutylguanidine with N,N’-methylenebisacrylamide, were reinforced with raw silk fibers, which can establish covalent bonds with the polyamidoamine matrix via reaction of the amine groups in the lysine residues with the acrylamide terminals of the M-AGM oligomer. Silk/M-AGM membranes were prepared by impregnating silk mats with M-AGM aqueous solutions and subsequent crosslinking by UV irradiation. The guanidine pendants of the M-AGM units imparted the ability to form strong but reversible interactions with oxyanions, including the highly toxic chromate ions. The potential of the silk/M-AGM membranes to purify Cr(VI)-contaminated water down to the drinkability level, that is, below 50 ppb, was tested by performing sorption experiments both in static (Cr(VI) concentration 20–2.5 ppm) and flow conditions (Cr(VI) concentration 10–1 ppm). After static sorption experiments, the Cr(VI)-loaded silk/M-AGM membranes could easily be regenerated via treatment with a 1 M sodium hydroxide solution. Dynamic tests performed using two stacked membranes and a 1 ppm Cr(VI) aqueous solution reduced Cr(VI) concentration down to 4 ppb. Remarkably, the use of renewable sources, the environmentally friendly preparation process, and the goal achieved meet eco-design requirements.