Hemp (Cannabrs sativa L.) seeds are wett known for their potential use as a source of nutrients, fiber, and bioactive compounds. A hemp protein isolate, prepared from defatted hemp ftour, was hydrotyzed by atcatase and ftavourzyme under specific conditions. The resutt¡ng hydrotysates were evatuated for the setection of potentially bioactive hemp protein hydrotysates (HPHs) owing to their DPPH scavenging and ferric reducing antioxidant power activity. ln vitro cell-free experiments ted to the identification of two bioact¡ve HPHs, HPH2OA and HPH60A + 15AF, which were used at 50 and 100 ¡rg mL-1 on BV-2 microgtial cetts in order to evatuate the anti-neuroinftammatory activ¡ties. Our results showed that HPH20A and HPH60A + 15AF down-regutated INF-ra tL-lp, and /L-6 mRNA transcriptionat tevels in LpSstimulated BV-2 microgtial cetls. ln addition, HPH2OA and HPH60A + 15AF up-regutated the gene expression of anti-inftammatory cytokine lL-10. This study suggests for the first time that HpHs may improve the neuroinflammatory and inftammatory states, supporting the nutraceutical value of hemp seeds.