The lysosome is a membrane-enclosed organelle in eukaryotic cells, which has basic pattern recognition for nutrient-dependent signal transduction. In Alzheimer's disease, the already declining autophagy-lysosomal function is exacerbated by an increased need for clearance of damaged proteins and organelles in aged cells. Recent evidence suggests that numerous diseases are linked to impaired autophagy upstream of lysosomes. In this way, a comprehensive survey on the pathophysiology of the disease seems necessary. Hence, in the first section of this review, we will discuss the ultimate findings in lysosomal signaling functions and how they affect cellular metabolism and trafficking under neurodegenerative conditions, specifically Alzheimer's disease. In the second section, we focus on how natural products and their derivatives are involved in the regulation of inflammation and lysosomal dysfunction pathways, including how these should be considered a crucial target for Alzheimer's disease therapeutics.