Biofilms are a major source of medical device-associated infections, due to their persistent growth and antibiotic resistance. Recent studies have shown that engineering surface nanoroughness has great potential to create antibacterial surfaces. In addition, stimulation of bacterial metabolism increases the efficacy of antibacterial agents to eradicate biofilms. In this study, we combined the antibacterial effects of nanorough topographies with metabolic stimulation (i.e., fructose metabolites) to further decrease bacterial growth on polyvinyl chloride (PVC) surfaces, without using antibiotics. We showed for the first time that the presence of fructose on nanorough PVC surfaces decreased planktonic bacteria growth and biofilm formation after 24 hours. Most importantly, a 60% decrease was observed on nanorough PVC surfaces soaked in a 10 mM fructose solution compared to conventional PVC surfaces. In this manner, this study demonstrated that bacteria growth can be significantly decreased through the combined use of fructose and nanorough surfaces and thus should be further studied for a wide range of antibacterial applications.