To minimize the possible usage of petroleum resources in the field of production of benzoxazines, the sustainable biological monomer magnolol has been utilized to synthesize bio-polybenzoxazines. Magnolol-based bio-thermosetting benzoxazines were synthesized using four different bio-amines, which were characterized for hydrophobicity, anti-microbial activity, cytotoxicity and anti-corrosion activity. Structural characterisation of synthesized bio-polybenzoxazines was carried out by ATR-FTIR and 1 H-NMR spectral analyzes. The polymerization behavior and thermal stability of synthesized magnolol-based monomers were studied by DSC and TGA analyzes, respectively. The TGA results indicate that poly(M-ffa) possesses excellent thermal stability with a char yield of 60% compared to that of other bio-thermosets. Anti-microbial studies suggest that M-oda exhibits the highest anti-microbial activity with inhibition zones of 25 and 20 mm against Staphylococcus aureus and Escherichia coli , respectively. As reported by an MTT assay, synthesized polybenzoxazines did not show any significant toxic effects on cell line 3T3-L1. It was observed that M-oda exhibits the least toxicity of 91.2% on 3T3-L1 cells at a minimum dosage of 5 μg mL −1 . All synthesized bio-polybenzoxazines exhibit excellent hydrophobicity with values of water contact angle ranging from 143 to 148°. A poly(M-oda)-coated cotton fabric retains significant durability even after repeated washing. All synthesized bio-thermosets showed an outstanding anti-corrosion property with a protection efficiency of over 95%. Using data obtained from different studies, it is suggested that magnolol-based thermoset polybenzoxazines could potentially be used as coatings to protect structures under marine environments and in other medically related uses due to their inherent characteristics to resist the growth of pathogens, low toxic nature, close to superhydrophobic behavior, and corrosion-resistant properties.