In this research study, two novel polymers including Schiff base were prepared by condensation reaction of polystyrene-A-NH2 with 5-nitro-2-thiophenecarboxaldehyde/or 5-(2-nitrophenyl)-2-furancarboxaldehyde. The synthesized polymers were evaluated using the elemental analysis, infrared spectroscopy (IR), gel permeation chromatography (GPC), thermal gravimetric analysis (TG/DTA). In addition, the antimicrobial and antimutagenic study of the polymers were reported. The antibacterial and antifungal activity were investigated using the diffusion method against pathogenic bacterial strains. PA-TC and PA-FC polymers exhibited the highest antimicrobial activity against the S. typhi H. and P. vulgaris, respectively. PA-FC polymer revealed the highest antifungal activity against C. albicans. The antimutagenic effects were evaluated using the sister chromatid exchange (SCE) and micronucleus (MN) methods against the sodium azide (NaN3) in human lymphocyte cells. The results demonstrated that the PA-FC polymer have strong antimutagenic properties, especially in the concentration of 20 μg/mL.