Recent instances of novel biological circuits that enable cells to gain biosynthetic skills demonstrate synthetic biology’s therapeutic potential. Synthetic biology is a branch of biology whose primary role is to build completely functional biological systems from the smallest basic elements such as DNA, proteins, and other organic molecules to complex bacteria. This review briefly mentions some novel way of synthetic strategies like bacterial modelling, two-component systems, synthetic peptide, and synthetic flavonoids used for targeting biofilm and drug-stable microbial communities. Bacterial modelling was mainly done in Escherichia coli and Mycoplasma using different strategies like introducing quorum sensing devices and CRISPR-mediated editing. Synthetic peptides are also one of the extensively studied ongoing areas which are produced from natural peptides taking as a template and altering amino acid position. Flavonoids are produced by two-step reaction and molecular hybridization methods. This kind of synthetic approach reported significant biofilm dispersion and lethal effects on clinically relevant bacteria like Pseudomonas aeruginosa, Staphylococcus aureus, E. coli, Acinetobacter baumannii, and Streptococcus species and Klebsiella pneumonia.