The article provides a comprehensive overview of the antimicrobial peptide melittin and its therapeutic potential. Melittin, derived from honeybee venom, is a cationic short peptide with amphipathic properties, capable of disrupting cell membranes and exhibiting antiviral, antitumor, and anti-inflammatory activities. The review highlights the structural characteristics of melittin, including its helix-hinge-helix motif and tetrameric structure, which contribute to its membrane-permeabilizing effects. Melittin's antiviral properties are discussed, particularly its ability to inhibit viral replication and reduce viral load in various infections, such as herpes simplex virus (HSV), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its antitumor effects are also explored, including its ability to modulate cell cycle, induce apoptosis, and inhibit angiogenesis and metastasis in various cancer types, such as colon, gastric, breast, and hepatocellular carcinoma. Additionally, melittin's anti-inflammatory properties are examined, showing its effectiveness in mitigating inflammation in conditions like arthritis, ulcerative colitis, acute liver failure, acne, atopic dermatitis, and periodontitis. The article also discusses strategies for enhancing melittin's therapeutic potential through nanocarrier systems, immuno-conjugation, structural regulation, and gene technology. However, the cytotoxicity of melittin against normal cells and red blood cells is noted as a limitation that needs to be addressed for its broader clinical application. Overall, the review underscores the promising therapeutic potential of melittin in various diseases and the ongoing research efforts to optimize its use.The article provides a comprehensive overview of the antimicrobial peptide melittin and its therapeutic potential. Melittin, derived from honeybee venom, is a cationic short peptide with amphipathic properties, capable of disrupting cell membranes and exhibiting antiviral, antitumor, and anti-inflammatory activities. The review highlights the structural characteristics of melittin, including its helix-hinge-helix motif and tetrameric structure, which contribute to its membrane-permeabilizing effects. Melittin's antiviral properties are discussed, particularly its ability to inhibit viral replication and reduce viral load in various infections, such as herpes simplex virus (HSV), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its antitumor effects are also explored, including its ability to modulate cell cycle, induce apoptosis, and inhibit angiogenesis and metastasis in various cancer types, such as colon, gastric, breast, and hepatocellular carcinoma. Additionally, melittin's anti-inflammatory properties are examined, showing its effectiveness in mitigating inflammation in conditions like arthritis, ulcerative colitis, acute liver failure, acne, atopic dermatitis, and periodontitis. The article also discusses strategies for enhancing melittin's therapeutic potential through nanocarrier systems, immuno-conjugation, structural regulation, and gene technology. However, the cytotoxicity of melittin against normal cells and red blood cells is noted as a limitation that needs to be addressed for its broader clinical application. Overall, the review underscores the promising therapeutic potential of melittin in various diseases and the ongoing research efforts to optimize its use.