This study presents a novel bio-based epoxy resin synthesized through a simple two-step method. The synthesis involved the combination of vanillin and 4,4′-diaminodiphenyl ether (ODA) to produce Schiff base alkaline compounds (SA-ODA), followed by conversion into epoxy resin (SA-ODA-EP) through an etherification reaction with epichlorohydrin (ECH). After curing with 4,4′-diaminodiphenylmethane (DDM), the resin exhibits significant flame-retardant properties, achieving a V-0 rating with a Limiting Oxygen Index (LOI) of 35.2 %. In comparison to E51/DDM, SA-ODA-EP/DDM demonstrated significant reductions in heat release and smoke generation. Furthermore, the resin displayed outstanding mechanical properties, including a glass transition temperature (Tg) of 188.9 °C and a high storage modulus. Notably, owing to its unique Schiff base alkaline structure, SA-ODA-EP/DDM exhibited excellent antibacterial performance against Escherichia coli, providing hygiene assurance for coatings. This study introduces a feasible synthetic approach for the preparation of epoxy resins with flame-retardant properties, superior mechanical performance, and antibacterial functionality, showcasing potential advancements in the field of coating material design.