In 2023, the FDA approved nine TIDES (peptides and oligonucleotides) for various therapeutic indications. Four oligonucleotides were approved for treating amyotrophic lateral sclerosis, geographic atrophy, primary hyperoxaluria type 1, and polyneuropathy of hereditary transthyretin-mediated amyloidosis. These oligonucleotides are chemically modified to enhance stability and therapeutic effectiveness. Some oligonucleotides also feature conjugation to driving ligands for targeted delivery. The approved peptides include linear, cyclic, and lipopeptides, with diverse applications. Notably, a peptide-based drug was granted its first orphan drug designation as a highly selective chemokine antagonist, and Rett syndrome received its first-ever core symptoms treatment, also peptide-based. The article analyzes the chemical structure, medical target, mode of action, administration route, and common adverse effects of these TIDES approvals. The successful approval of TIDES drugs highlights the progress in therapeutic development and the collaboration between academia and industry. Oligonucleotides are gaining attention for their potential in treating rare genetic disorders, while peptides are showing promise in challenging therapeutic tasks, such as mobilizing hematopoietic stem cells.In 2023, the FDA approved nine TIDES (peptides and oligonucleotides) for various therapeutic indications. Four oligonucleotides were approved for treating amyotrophic lateral sclerosis, geographic atrophy, primary hyperoxaluria type 1, and polyneuropathy of hereditary transthyretin-mediated amyloidosis. These oligonucleotides are chemically modified to enhance stability and therapeutic effectiveness. Some oligonucleotides also feature conjugation to driving ligands for targeted delivery. The approved peptides include linear, cyclic, and lipopeptides, with diverse applications. Notably, a peptide-based drug was granted its first orphan drug designation as a highly selective chemokine antagonist, and Rett syndrome received its first-ever core symptoms treatment, also peptide-based. The article analyzes the chemical structure, medical target, mode of action, administration route, and common adverse effects of these TIDES approvals. The successful approval of TIDES drugs highlights the progress in therapeutic development and the collaboration between academia and industry. Oligonucleotides are gaining attention for their potential in treating rare genetic disorders, while peptides are showing promise in challenging therapeutic tasks, such as mobilizing hematopoietic stem cells.