Peptide-drug conjugates (PDCs) are a promising new class of targeted cancer therapeutics that utilize peptide moieties as carriers for cytotoxic payloads, connected by cleavable or non-cleavable linkers. These conjugates can retain their integrity in the bloodstream and release drugs specifically at the tumor microenvironment, offering advantages such as specificity, selectivity, and enhanced penetration. This review summarizes the types of cell-targeting peptides (CTPs) and cell-penetrating peptides (CPPs) used in PDCs, along with techniques to overcome limitations in peptide chemistry for their development. It also discusses advancements in linker chemistry and the mechanisms of action of PDCs. PDCs are designed to deliver cytotoxic payloads to cancer cells with high specificity, reducing off-target toxicity. They are compared to antibody-drug conjugates (ADCs), which have faced challenges such as rapid plasma clearance and off-target toxicity. PDCs offer improved stability and targeted delivery, making them a promising alternative. The review highlights the importance of linker chemistry in ensuring the stability of PDCs in the bloodstream and their efficient release at the tumor site. Various strategies are discussed to improve the chemical and enzymatic stability of peptides, including cyclization, the use of D-amino acids, and chemical modifications such as PEGylation. These modifications enhance the half-life of peptides in the bloodstream, improve their bioavailability, and reduce renal clearance. Additionally, nanomicroformulations and peptide-based nanoparticles are explored as platforms for targeted drug delivery. The review also discusses the application of PDCs in various therapeutic areas beyond oncology, including diabetes, rheumatoid arthritis, and COVID-19. Cell-targeting peptides (CTPs) and cell-penetrating peptides (CPPs) are classified based on their ability to bind to specific receptors on cancer cells, facilitating targeted drug delivery. Neuropeptide Y (NPY) and somatostatin peptides are highlighted as examples of peptides with potential in PDCs due to their specific binding to receptors on cancer cells. Overall, PDCs represent a promising approach for targeted cancer therapy, offering improved efficacy and reduced side effects compared to traditional chemotherapy. The review emphasizes the importance of continued research in peptide chemistry, linker technology, and targeted delivery systems to further enhance the therapeutic potential of PDCs.Peptide-drug conjugates (PDCs) are a promising new class of targeted cancer therapeutics that utilize peptide moieties as carriers for cytotoxic payloads, connected by cleavable or non-cleavable linkers. These conjugates can retain their integrity in the bloodstream and release drugs specifically at the tumor microenvironment, offering advantages such as specificity, selectivity, and enhanced penetration. This review summarizes the types of cell-targeting peptides (CTPs) and cell-penetrating peptides (CPPs) used in PDCs, along with techniques to overcome limitations in peptide chemistry for their development. It also discusses advancements in linker chemistry and the mechanisms of action of PDCs. PDCs are designed to deliver cytotoxic payloads to cancer cells with high specificity, reducing off-target toxicity. They are compared to antibody-drug conjugates (ADCs), which have faced challenges such as rapid plasma clearance and off-target toxicity. PDCs offer improved stability and targeted delivery, making them a promising alternative. The review highlights the importance of linker chemistry in ensuring the stability of PDCs in the bloodstream and their efficient release at the tumor site. Various strategies are discussed to improve the chemical and enzymatic stability of peptides, including cyclization, the use of D-amino acids, and chemical modifications such as PEGylation. These modifications enhance the half-life of peptides in the bloodstream, improve their bioavailability, and reduce renal clearance. Additionally, nanomicroformulations and peptide-based nanoparticles are explored as platforms for targeted drug delivery. The review also discusses the application of PDCs in various therapeutic areas beyond oncology, including diabetes, rheumatoid arthritis, and COVID-19. Cell-targeting peptides (CTPs) and cell-penetrating peptides (CPPs) are classified based on their ability to bind to specific receptors on cancer cells, facilitating targeted drug delivery. Neuropeptide Y (NPY) and somatostatin peptides are highlighted as examples of peptides with potential in PDCs due to their specific binding to receptors on cancer cells. Overall, PDCs represent a promising approach for targeted cancer therapy, offering improved efficacy and reduced side effects compared to traditional chemotherapy. The review emphasizes the importance of continued research in peptide chemistry, linker technology, and targeted delivery systems to further enhance the therapeutic potential of PDCs.