This Research Aimed to Discuss the Protective Mechanism of Lycium barbarum Polysaccharides (LBPs) Against Ethanol (EtOH)-caused Hepatocellular Damage. Normal human hepatocytes (L-02 cells) were processed with 100 μg/mL EtOH to simulate liver injury, followed by treatment with LBPs at different concentrations (12, 24, 48 μg/mL) to determine the optimal dose. Cells were divided into the control, EtOH, EtOH+LBP-treated, and EtOH+LBP-treated with siRNA against PPAR-α groups. To evaluate treatment effects, the MTT assay was utilized for measuring cell viability, succeeded by the assessment of liver injury markers (ALT, AST, TG) and inflammatory cytokines (IL-1β, TNF-α, and IL-6). Besides, the GSDMD, NLRP-3, caspase-1, and PPAR-α protein levels were analyzed via western blotting. Relative to the Control group, EtOH exposure remarkably decreased cell viability, increased TG, AST, and ALT levels (p < 0.01), and induced cell damage and lipid accumulation. It also elevated inflammatory cytokine levels and triggered pyroptosis (p < 0.01). However, LBP treatment alleviated EtOH-induced damage, reduced lipid accumulation, inhibited pyroptosis-related protein expression, suppressed inflammatory responses, and upregulated PPAR-α protein expression (p < 0.01). LBPs can alleviate EtOH-induced L-02 cell injury, lipid accumulation, inflammatory response, and pyroptosis. The mechanism is possibly associated with inhibiting NLRP-3/caspase-1-mediated cell pyroptosis by activating PPAR-α expression, thus protecting hepatocytes from injury.