Neurodegenerative diseases pose significant challenges to global health-care systems, highlighting the urgent need for effective therapeutic strategies. Apigenin (API), a natural compound derived from various plant sources, has emerged as a potential treatment option due to its neuroprotective properties. This review article provides a comprehensive overview of API, focusing on its definition, natural sources, pharmacokinetics, and bioavailability, mechanisms of action, safety, and tolerability profile. API protects neurons in many ways, including its antioxidant activity, anti-inflammatory properties, ability to change cellular signaling pathways, ability to stop proteins from misfolding and sticking together, and ability to improve mitochondrial function. In vitro studies have demonstrated that API attenuates oxidative stress, inhibits the formation of protein aggregates, and suppresses neuroinflammation. Animal models, such as transgenic mice, rat models, and non-human primates, have provided valuable insights into the potential therapeutic benefits of API, including improved cognitive function, mitigation of motor impairments, and preservation of neuronal integrity. API’s safety and tolerability profile appears favorable based on preclinical and clinical studies, with minimal reported adverse effects. However, further investigation is required to determine optimal dosing regimens and assess potential drug interactions. In addition, while current treatment options for neurodegenerative diseases primarily focus on symptom management, API holds promise as a disease-modifying agent.