Andrographolide (ANDRO), a bitter diterpene lactone found in Andrographis paniculata (Burm.f.) Nees, possesses several biological effects such as antioxidant, anti-inflammatory, and organo-protective effects. Scientific reports suggest that it also has neuroprotective capacity in various test systems. The purpose of this review was to synthesize the neuropharmacological properties of ANDRO and highlight the molecular mechanisms of action that highlight these activities. A careful search was done in PubMed and Google Scholar databases using specific keywords. Findings suggest that ANDRO possess neuroprotective, analgesic, and antifatigue effects. Prominent effects were stated on neuro-inflammation, cerebral ischemia, Alzheimer’s and Parkinson’s diseases, multiple sclerosis, and brain cancer in mice and rats. Furthermore, ANDRO and its derivatives can enhance memory and learning capacity in experimental animals (rats) without causing any toxicity in the brain. Thus, ANDRO may be one of the most promising plant-based psychopharmacological lead compounds for new drug development.