Trigonelline (TRG), a natural polar hydrophilic alkaloid found in plants like green coffee beans and fenugreek seeds, exhibits a wide range of pharmacological activities and therapeutic effects. This review systematically summarizes its potential as a therapeutic agent, focusing on its mechanisms of action. TRG acts on multiple molecular targets, including Nrf2, PPARγ, GSK, tyrosinase, NGF, estrogen receptor, and neurotransmitter receptors. Mechanistically, it helps maintain and restore metabolic homeostasis of glucose and lipids, counteracts inflammation by inhibiting pro-inflammatory factors and reducing oxidative stress, and modulates autophagy. These actions result in diverse therapeutic benefits, including neuroprotection, neuromodulation, cardiovascular protection, liver and kidney protection, anti-cancer effects, and anti-inflammatory and antimicrobial properties. TRG shows promise in treating chronic metabolic diseases, age-related disorders, and various pathological conditions. However, further research is needed to define its specific targeting molecules, disentangle underlying mechanisms, and validate its efficacy in clinical trials.Trigonelline (TRG), a natural polar hydrophilic alkaloid found in plants like green coffee beans and fenugreek seeds, exhibits a wide range of pharmacological activities and therapeutic effects. This review systematically summarizes its potential as a therapeutic agent, focusing on its mechanisms of action. TRG acts on multiple molecular targets, including Nrf2, PPARγ, GSK, tyrosinase, NGF, estrogen receptor, and neurotransmitter receptors. Mechanistically, it helps maintain and restore metabolic homeostasis of glucose and lipids, counteracts inflammation by inhibiting pro-inflammatory factors and reducing oxidative stress, and modulates autophagy. These actions result in diverse therapeutic benefits, including neuroprotection, neuromodulation, cardiovascular protection, liver and kidney protection, anti-cancer effects, and anti-inflammatory and antimicrobial properties. TRG shows promise in treating chronic metabolic diseases, age-related disorders, and various pathological conditions. However, further research is needed to define its specific targeting molecules, disentangle underlying mechanisms, and validate its efficacy in clinical trials.