Lycium ruthenicum Murr. (LR) is a perennial shrub commonly used as a nutritional food and medicine. Herein, we identified 12 anthocyanins from LR, with petunidin derivatives constituting approximately 97% of the total anthocyanin content. Furthermore, the potential mechanism of anthocyanins exerting neuroprotective effects in d-galactose (d-gal)-treated rats was explored. Behavioral results showed that anthocyanins relieved d-gal-induced memory disorder. Additionally, anthocyanins reduced receptor for advanced glycation end products (RAGE) and suppressed oxidative stress caused by d-gal. Anthocyanins suppressed microgliosis and astrocytosis and reduced the overexpression of nuclear factor kappa B (NF-κB), interleukin-1-β (IL-1β), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α). Moreover, anthocyanins lowered C-jun N-terminal kinase ( p-JNK), caspase-3 levels, and the B-cell lymphoma 2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) ratio. Thus, anthocyanins from LR attenuated memory disfunction, neuroinflammation, and neurodegeneration caused by d-gal, possibly through the RAGE/NF-κB/JNK pathway, representing a promising, safe candidate for prevention and therapy of neurodegenerative diseases.