Neurodegeneration is the progressive loss of neurons that results in neurodegenerative diseases (NDs). Currently, there are few effective treatments for NDs, such as Alzheimer’s disease, Parkinson’s disease, Multiple sclerosis, and Huntington’s disease, which involve gradual neuronal death and cognitive deterioration. Alkaloids are naturally occurring molecules with a variety of biological properties. Recent studies have shown that these compounds may be able to modulate signaling pathways linked to many diseases. Alkaloids, with their antioxidant and neuroprotective properties, have the potential to treat neurodegeneration by simultaneously affecting multiple disease parts and modifying neuroinflammatory responses. These interact with various molecular targets, such as transcription factors, receptors, and enzymes involved in neuronal survival and homeostasis. The development of complete therapeutic techniques can be facilitated by alkaloid-based multi-target approaches, which challenge the intricate nature of neurodegenerative pathways. The review highlights the potential of alkaloid-based multi-target strategies in treating NDs and calls for further research to understand their clinical applications fully. Future studies should focus on finding neuroprotective alkaloids, investigating their mechanisms, and evaluating their therapeutic potential. Understanding how alkaloids interact with key pathways in NDs is essential for developing effective therapies.