In 2023, the FDA approved nine TIDES (peptides and oligonucleotides), including four oligonucleotides for various disorders such as amyotrophic lateral sclerosis, geographic atrophy, primary hyperoxaluria type 1, and polyneuropathy of hereditary transthyretin-mediated amyloidosis. These oligonucleotides have chemically modified structures to enhance stability and therapeutic effectiveness. Some are conjugated to ligands for targeted delivery. The approved peptides include linear, cyclic, and lipopeptides with diverse applications. The FDA granted its first orphan drug designation for a peptide-based drug, a highly selective chemokine antagonist, and Rett syndrome found its first-ever core symptoms treatment, also peptide-based. The review analyzes the TIDES approved in 2023 based on their chemical structure, medical target, mode of action, administration route, and common adverse effects. The four oligonucleotides include tofersen, avacincaptad pegol, nedosiran, and eplontersen, each with specific mechanisms of action and delivery methods. The peptides include flotufolastat F 18, motixafortide, rezafungin, trofinetide, and zilucoplan, each with unique therapeutic applications and side effects. The review highlights the progress in TIDES development, the collaboration between academia and industry, and the potential of peptides and oligonucleotides in treating rare genetic disorders. The study underscores the importance of chemical modifications and targeted delivery in improving the efficacy and safety of these therapies.In 2023, the FDA approved nine TIDES (peptides and oligonucleotides), including four oligonucleotides for various disorders such as amyotrophic lateral sclerosis, geographic atrophy, primary hyperoxaluria type 1, and polyneuropathy of hereditary transthyretin-mediated amyloidosis. These oligonucleotides have chemically modified structures to enhance stability and therapeutic effectiveness. Some are conjugated to ligands for targeted delivery. The approved peptides include linear, cyclic, and lipopeptides with diverse applications. The FDA granted its first orphan drug designation for a peptide-based drug, a highly selective chemokine antagonist, and Rett syndrome found its first-ever core symptoms treatment, also peptide-based. The review analyzes the TIDES approved in 2023 based on their chemical structure, medical target, mode of action, administration route, and common adverse effects. The four oligonucleotides include tofersen, avacincaptad pegol, nedosiran, and eplontersen, each with specific mechanisms of action and delivery methods. The peptides include flotufolastat F 18, motixafortide, rezafungin, trofinetide, and zilucoplan, each with unique therapeutic applications and side effects. The review highlights the progress in TIDES development, the collaboration between academia and industry, and the potential of peptides and oligonucleotides in treating rare genetic disorders. The study underscores the importance of chemical modifications and targeted delivery in improving the efficacy and safety of these therapies.