Biofilm is a powerful barrier that significantly enhances the pathogenicity of bacteria and the development of multidrug resistance. Nanoparticles (NPs) coupled with biomolecules provide a novel approach to addressing this issue. This review briefly discusses the current trends in Biomolecule-Conjugated NPs combined with enzymes, antibiotics, biosurfactants, and natural bioactive compounds as antibiofilm agents emphasizing their superior antibiofilm activity. This conjugation enhances bioavailability, lowers toxicity, requires smaller dosage, and reduces complications caused by infections associated with biofilms. These conjugated systems offer an avenue for industrial, ecological, and medical applications. By increasing the variety of these conjugation techniques, innovative approaches to biofilm-related problems will become possible, with significant advantages for healthcare and other fields.