Catheter-associated urinary tract infections (CAUTIs) are nosocomial infections, causing more than one million cases per year. CAUTIs cause serious health issues; in addition, the cost of replacement of the device constrains the employment of urological devices. Therefore, there is an urgent need to develop novel biomaterials for use in catheters. In this study, poly hydroxyethyl-methacrylate p(HEMA) and drugs-loaded p(HEMA) with ampicillin trihydrate (AMP), levofloxacin (LVX), and drug combinations were prepared using free radical polymerization. The characterization of the dried films included the determination of glass transition temperature (Tg), ultimate tensile strength, elongation percentage, and Young’s modulus. Formulation toxicity, antimicrobial activity, and biofilm-formation ability were tested. Decreases in Tg value, U.T.S., and Young’s modulus, and an increase in elongation percentage were observed in AMP-loaded p(HEMA). Different ratios of drug combinations increased the Tg values. The films exhibited a cell viability higher than 80% on HEK 293 cells. Antimicrobial activity increased when p(HEMA) was loaded with LVX or a combination of LVX and AMP. Biofilm-forming ability reduced after the addition of antimicrobial agents to the films. p(HEMA) impregnated with AMP, LVX, and drug combinations showed significantly increased antimicrobial activity and decreased biofilm-forming ability compared with p(HEMA), in addition to the effects on (HEMA) mechanical properties.