SIRT1, a NAD⁺-dependent class III deacetylase, plays a critical role in various diseases, making it a promising therapeutic target. SRT2104, a highly specific and potent SIRT1 activator, is currently in clinical trials. This review evaluates SRT2104's emerging roles in disease treatment, focusing on its molecular mechanisms, preclinical research, and clinical trials. SRT2104 exhibits strong binding affinity with SIRT1, demonstrating significant therapeutic potential in modulating metabolic and longevity-related pathways. It has shown favorable pharmacokinetic properties and good tolerability in clinical trials. SRT2104 has been investigated for its potential in neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's, as well as in brain ischemia/reperfusion injury, optic nerve degenerative diseases, depression, diabetic complications, lipid metabolism, cardiovascular disease, musculoskeletal diseases, and chronic obstructive pulmonary disease (COPD). In neurodegenerative diseases, SRT2104 has shown protective effects by modulating SIRT1 activity, reducing oxidative stress, and promoting autophagy. In diabetes, SRT2104 has been shown to improve endothelial dysfunction and reduce oxidative stress. In COPD, SRT2104 has been found to alleviate emphysema and improve lung function by enhancing SIRT1 expression and reducing cellular senescence. In depression, SRT2104 has shown antidepressant effects by modulating microglial polarization and reducing inflammatory responses. In musculoskeletal diseases, SRT2104 has been shown to enhance bone health and alleviate skeletal muscle atrophy. Overall, SRT2104 shows significant therapeutic potential in various diseases, with ongoing clinical trials to further explore its applications.SIRT1, a NAD⁺-dependent class III deacetylase, plays a critical role in various diseases, making it a promising therapeutic target. SRT2104, a highly specific and potent SIRT1 activator, is currently in clinical trials. This review evaluates SRT2104's emerging roles in disease treatment, focusing on its molecular mechanisms, preclinical research, and clinical trials. SRT2104 exhibits strong binding affinity with SIRT1, demonstrating significant therapeutic potential in modulating metabolic and longevity-related pathways. It has shown favorable pharmacokinetic properties and good tolerability in clinical trials. SRT2104 has been investigated for its potential in neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's, as well as in brain ischemia/reperfusion injury, optic nerve degenerative diseases, depression, diabetic complications, lipid metabolism, cardiovascular disease, musculoskeletal diseases, and chronic obstructive pulmonary disease (COPD). In neurodegenerative diseases, SRT2104 has shown protective effects by modulating SIRT1 activity, reducing oxidative stress, and promoting autophagy. In diabetes, SRT2104 has been shown to improve endothelial dysfunction and reduce oxidative stress. In COPD, SRT2104 has been found to alleviate emphysema and improve lung function by enhancing SIRT1 expression and reducing cellular senescence. In depression, SRT2104 has shown antidepressant effects by modulating microglial polarization and reducing inflammatory responses. In musculoskeletal diseases, SRT2104 has been shown to enhance bone health and alleviate skeletal muscle atrophy. Overall, SRT2104 shows significant therapeutic potential in various diseases, with ongoing clinical trials to further explore its applications.