Background: One of the foremost causes of microbial infections and propagation is improper sanitation and hygiene maintained in public places. Accumulation of stains and microbes results in the spread of infections. Also, due to the extensive use of non-renewable materials like petrochemicals, etc., there is an increasing demand for sustainable growth in the coating industries. Currently, there is no such technology that tackles this problem. Methods: Our present work aims to find a prolonged solution for these problems for the first time by synthesizing and formulating bio-based coatings with inherent antimicrobial properties and durable surface properties with a fast air-curing system. A formulation of alkyd and polyesteramide resins from castor, neem, and karanja oils was crosslinked with isocyanates to form the surface coatings. An esterification reaction of castor oil monoglyceride and phthalic anhydride synthesized the castor oil alkyd resin. The corresponding neem and karanja oil polyesteramides were synthesized by amidation with diethanolamine, followed by an esterification reaction. Results: The coatings exhibit an antimicrobial efficacy of 74%–84% against both Gram-positive and Gram-negative bacteria and contain 76.5% bio-based content. Factors such as thermal stability, physicochemical properties, and chemical and solvent stability were studied. After 24 h of inoculation with 40% polyesteramide resin (AMRESN-4), E. coli and S. aureus CFU values decreased from 6 × 10⁵ to 0.28 × 10⁵ CFU/g and from 5.7 × 10⁵ to 0.26 × 10⁵ CFU/g, respectively. These bio-based coatings are particularly suited for environments requiring high durability and antimicrobial protection, such as food-processing facilities, healthcare settings, and public restrooms.