Peptides are becoming more and more significant as drug candidates. Small peptides that are found in nature frequently have important medicinal characteristics. In recent years, peptide-based drug delivery has seen enormous advancements in therapeutic applications due to the considerable adaptability and inherent high affinity of peptides for their target sites. Although the synthesis of peptides has a long history, it still has a number of drawbacks, including high costs, significant waste production, and a need for potentially harmful reagents and solvents. Peptide medication and its therapeutic usage have progressed with time and continue to progress through medication advancements and technological changes. Peptides have been synthesized and altered utilizing chemical and biological techniques, as well as innovative design and delivery technologies, which have assisted in eliminating the inherent limitations of peptides and permitted the continuous growth of this sector. Solid-phase peptide synthesis (SPPS) is the peptide synthesis technique used for novel drug delivery systems. In order to improve the therapeutic benefits of peptide-based therapeutics, SPPS aims to produce large peptides that can be readily metabolized and modified for targeted drug delivery. This review article discusses several aspects of Advance Solid Phase Synthesis of therapeutic Peptides including their historical development, current trends, and future perspectives. Recently, 4% of overall approved drugs are peptide-based drugs or their derivatives. By utilizing various advanced synthesizers, new methods for automated peptide synthesis can meet the growing need for this process. In the future, the projected demand for polypeptides as biological products will surely promote and increase interest in these developments.