Wolfberry (Lycium barbarum L.) is a medicinal herb with anti-aging and neuroprotective effects. The purpose of this study was to explore the enhanced neuroprotective effects of red wolfberry water extract (RW), and brown wolfberry water extract (BBW). The reduced percentage of reducing sugar in BBW was shown to be 62.8%, 64.3%, 39.8%, and 11.6% for glucose, fructose, maltose, and lactose compared to those of RW, as well as free amino acids. And the contents of total phenols and total flavonoids were increased by 62.0% and 51.0%. Melanoidins (1.00%) were first isolated from BBW. RW and BBW increased anti-stress abilities (oxidative stress: 24.2% vs. 35.7%, and heat stress: 17.78% vs. 57.57%) while decreasing the reactive oxygen species (ROS) levels in vivo. RW and BBW reduced the rate of paralysis and odor cognitive deficits. At the same time, RW and BBW reduced the number of fluorescent spots of Aβ::GFP. The RW and BBW activated autophagy by upregulating the gene levels (bec-1, lgg-1, lgg-2, unc-51, vps-34, atg-5, atg-18, and sqst-1). Additionally, BBW promoted the nuclear-cytoplasmic ratio of DAF-16::GFP and fluorescence intensity of SOD-3::GFP by 39.4 and 1.16 fold. This study laid a new insight for exploring the Maillard reaction in improving the anti-Alzheimer's disease (AD) activity of wolfberry.