The present study successfully demonstrated the neuroprotective effects of purified Lycium barbarum polysaccharide (LBPS02) against glutamate (L‑Glu)‑induced differentiated PC12 (DPC12) cell apoptosis. Purified polysaccharide was obtained by using a diethylaminoethyl‑52 cellulose anion exchange column and a Sepharose G‑100 column. During identification and characterization, LBPS02 was validated to be a fraction with 68 kDa molecular weight, and with a structure containing 1→3, 1→4 and 1→6 linkages. Data further revealed that LBPS02 pretreatment effectively improved cell viability, reduced apoptosis rate, and restored the mitochondrial dysfunction in L‑Glu‑exposed cells. LBPS02 suppressed L‑Glu‑induced reactive oxygen species (ROS accumulation in DPC12 cells. N‑acetylcysteine, a ROS inhibitor, strongly enhanced the efficacy of LBPS02. Furthermore, LBPS02 normalized the levels of anti‑apoptotic proteins, and regulated the phosphorylation of extracellular signal‑regulated kinases (ERKs) and protein kinase B (Akt) in L‑Glu‑explored DPC12 cells. In conclusion, LBPS02‑mediated neuroprotective effects are at least partially associated with the modulation of Akt and ERKs, and the subsequent inhibition of the mitochondrial apoptotic pathway. LBPS02 may be a candidate for neurodegenerative disease treatment.