The synthesis of Schiff bases of chitosan is performed by the reaction of chitosan with different heteroaryl aldehydes, i.e., furfuraldehyde, thiophene-2-carboxylaldehyde, pyrrole-2-carboxylaldehyde, pyridine-2-carboxylaldehyde, pyridine-3-carboxylaldehyde and pyridine-4-carboxylaldehyde. The structural characterizations of the biopolymeric Schiff bases are executed by 1H NMR spectroscopy, Fourier transform infrared spectroscopy and elemental analysis (C, H, N). The 1H NMR spectroscopy is also used to determine the degree of deacetylation of chitosan as well as the degree of substitution (DS) of Schiff bases and DS found to be varying from 58 to 74%. Thermogravimetry studies of chitosan and its Schiff base polymers show that they have nearly the same decomposition temperature and hence equally thermally stable. The model-free multiple heating rate method Kissinger–Akahira–Sunose has been employed for the thermal degradation kinetics of the most potent antimicrobial compound ChSB-6. The antimicrobial activities of chitosan and its Schiff bases are tested against different pathogenic bacteria: Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Aspergillus niger, and results shows that the activities of the Schiff bases of chitosan are found to be stronger than that of chitosan.