Contamination of food with pathogenic microorganisms is a serious food safety challenge. Microbial spoilage of food products can also result in significant food loss during the production, processing, and handling of food. Although chemical sanitizers have been commonly used for disinfection of food-contact surfaces, the chemical residues in the food system may pose health and environmental concerns. In addition, indiscriminate use of these chemical sanitizers can increase the risk of developing antimicrobial resistance. The thermal processing of food has long been considered a standard method for reducing the microbial risk in food products. However, high energy consumption, thermal degradation of nutrients, and quality loss of the food products during thermal processes still remain unresolved. Furthermore, thermal technologies can not address the required food safety needs across diverse food systems, including minimally processed products. In addition, there is a lack of tools to prevent microbial contamination of food products from the environment, including food-contact surfaces. Therefore, a holistic approach that can reduce the microbial risk of food products and food-handling surfaces on a farm-to-fork basis while ensuring the sustainability of food is needed. In this research, a bio-based antimicrobial system was developed using cell-based antimicrobial microcarriers, food-grade surfactants, and plant byproduct-derived antimicrobial extracts. In addition, the techno-economic feasibility of combining the plant byproduct-derived antimicrobial extracts with a non-thermal, low-energy process for a food processing application was assessed. A bio-based antimicrobial delivery system composed of yeast-based microcarriers enabled targeted delivery of the essential oils against bacterial biofilms, and the facilitated release of the encapsulated essential oils effectively inactivated bacterial biofilms formed on food-contact surfaces. An antimicrobial coating formulation composed of hydrophobic yeast cells and food-grade, non-ionic surfactant was sprayed on food-contact surfaces, persisted on the surfaces under mechanical stresses, and effectively reduced the surface-mediated, microbial cross-contamination of food products. Antimicrobial extracts obtained from olive byproducts contained diverse antimicrobial phenolic compounds, and strong antimicrobial synergism was observed between these phenolic components through multiple modes of action. In addition, the combined treatment of the olive byproduct extract with UV-A light induced synergistic inactivation of bacterial pathogens in juice products, and the techno-economic analysis demonstrated the technical and economic viability of this combined process for juice pasteurization applications. This research offers a holistic solution that integrates bio-based approaches to address some of the key challenges to enhance the safety and sustainability of food products. The bio-based antimicrobial system, consisting of cell-based microcarriers, bio-based coating formulations, and plant byproduct-derived extracts can provide safe and environmentally friendly control strategies against pathogenic and spoilage microorganisms on food and food-contact surfaces. Furthermore, the technical and economic feasibility demonstrated by the synergistic process of plant byproduct-derived extracts with a low-energy, non-thermal processing technology provides essential information for translating this combined process into actual food processing applications. Overall, the bio-based antimicrobial system developed in this research will help enhance the microbial safety and sustainability of food systems.