Trigonelline (TRG) is a natural alkaloid found in plants like green coffee beans and fenugreek seeds. It acts on multiple molecular targets, including Nrf2, PPARγ, GSK, tyrosinase, NGF, estrogen receptor, and several neurotransmitter receptors. TRG modulates glucose and lipid metabolism, reduces inflammation and oxidative stress, and exhibits neuroprotective, cardioprotective, hepatoprotective, nephroprotective, and anti-cancer effects. It also shows antimicrobial, antiviral, and antifungal activities. TRG is safe, with no toxicity observed in acute studies, and has a good safety profile. It can improve insulin sensitivity, reduce diabetic complications, and protect against various diseases. However, the exact mechanisms of TRG's effects, particularly its ability to cross the blood-brain barrier, remain unclear. Further research is needed to fully understand its therapeutic potential and mechanisms.Trigonelline (TRG) is a natural alkaloid found in plants like green coffee beans and fenugreek seeds. It acts on multiple molecular targets, including Nrf2, PPARγ, GSK, tyrosinase, NGF, estrogen receptor, and several neurotransmitter receptors. TRG modulates glucose and lipid metabolism, reduces inflammation and oxidative stress, and exhibits neuroprotective, cardioprotective, hepatoprotective, nephroprotective, and anti-cancer effects. It also shows antimicrobial, antiviral, and antifungal activities. TRG is safe, with no toxicity observed in acute studies, and has a good safety profile. It can improve insulin sensitivity, reduce diabetic complications, and protect against various diseases. However, the exact mechanisms of TRG's effects, particularly its ability to cross the blood-brain barrier, remain unclear. Further research is needed to fully understand its therapeutic potential and mechanisms.