Cross-linked and flexible poly(vinyl acetone ketal) (PV-A-K) films have been prepared as a result of ketalization reaction and monolith formation of poly(vinyl alcohol) (PVA), which has the feature of forming films quickly and is frequently used in biological fields. In this novel method, flexible PV-A-K films have been produced simply and in a short time accompanied by monolith formation without any catalyst in acetone. The effect of acetone ratio on the physical properties (i.e., swelling and mechanical properties) of such formations has been investigated to reveal significant influences of it. In addition, zinc oxide (ZnO) nanoparticles synthesized via the solvothermal method have been doped into PV-A-K films during film preparation. The prepared PV-A-K and ZnO doped PV-A-K films have been characterized with SEM, XRD, and FT-IR. Their mechanical properties have been investigated with a universal mechanical test machine. The acetone ratio is quite effective both on the porosity and stress/strain properties of the films. Antibacterial activities of the films are evaluated against four different strains (E. coli, S. aureus, P. aeruginosa, and E. faecalis) via the disk diffusion method. The films are selectively effective against S. aureus. These highly flexible and elastic films have great potential for biomedical applications, wound dressing, and antibacterial surface preparation.