The article reviews novel therapeutic agents for the management of diabetes mellitus (DM), highlighting their potential in addressing the complex pathogenesis of the disease. DM is characterized by insulin secretion decline and peripheral resistance, with various pathogenic determinants such as adipocyte insulin resistance, increased glucagon secretion, and neurotransmitter dysfunction. Current therapeutic interventions focus primarily on glycemic control, but long-term use of conventional anti-diabetic drugs leads to side effects, necessitating the development of novel drugs. The review discusses stem cell therapy, transdermal drug delivery systems (TDDS), nanotechnology, and novel candidate drugs like fucoidan, SGLT-2 inhibitors, statins, and quercetin. It also explores immunological approaches, ethnomedicine, and dietetics as potential strategies for managing DM. The article emphasizes the need for further research to identify and develop effective and safe novel therapeutic agents to combat the global diabetes epidemic.The article reviews novel therapeutic agents for the management of diabetes mellitus (DM), highlighting their potential in addressing the complex pathogenesis of the disease. DM is characterized by insulin secretion decline and peripheral resistance, with various pathogenic determinants such as adipocyte insulin resistance, increased glucagon secretion, and neurotransmitter dysfunction. Current therapeutic interventions focus primarily on glycemic control, but long-term use of conventional anti-diabetic drugs leads to side effects, necessitating the development of novel drugs. The review discusses stem cell therapy, transdermal drug delivery systems (TDDS), nanotechnology, and novel candidate drugs like fucoidan, SGLT-2 inhibitors, statins, and quercetin. It also explores immunological approaches, ethnomedicine, and dietetics as potential strategies for managing DM. The article emphasizes the need for further research to identify and develop effective and safe novel therapeutic agents to combat the global diabetes epidemic.