Antisense oligonucleotide therapy is a dominant drug discovery approach that can explicitly modify protein synthesis through numerous mechanisms. The limitations of antisense oligonucleotide (ASO) therapy in delivery strategies have been overcome in recent years with different ligands carriers, as well as, through nanocarriers. ASO therapy was successfully applied towards targeting a wide range of therapeutic areas. There is an expanding enthusiasm in extending the utilization of antisense compounds to numerous different diseases due to their safe and potential therapeutic outcomes. Thus, the present review attempted to elaborate on the fundamental idea of antisense technology, approaches, and safe and effective delivery methods.