Contamination of food by bacterial pathogens is one of the biggest concerns in the food industry as it can result in serious human illnesses and death. Approaches to eliminate bacteria from outer surfaces of food products would be an effective way to safeguard against bacterial contamination. Nanopillars found on natural surfaces have been shown to mechanically damage cell membranes of foodborne bacteria. Therefore, fabricating bio-inspired mechano-bactericidal nanostructures into food packaging and processing materials could be a promising strategy to reduce surface bacterial contamination, to improve food safety. In this review, we summarize the formation of natural and synthetic nanopillared surfaces and their mechanism of action, and highlight the factors that influence their mechano-bactericidal activities.