The brain is vulnerable to oxidative stress and inflammation that can occur as a result of aging or neurodegenerative diseases. Our work has sought to identify natural products that regulate heme oxygenase (HO)‐1 and to determine their mechanism of action in neurodegenerative diseases. KCHO‐1 is a novel herbal therapeutic containing 30% ethanol (EtOH) extracts from nine plants. In this study, we investigated the antineuroinflammatory effects of KCHO‐1 in lipopolysaccharide‐ (LPS‐) treated mouse BV2 microglia. KCHO‐1 inhibited the protein expression of inducible nitric oxide synthase (iNOS), iNOS‐derived nitric oxide (NO), cyclooxygenase‐ (COX‐) 2, and COX‐2‐derived prostaglandin E2 (PGE₂) in LPS‐stimulated BV2 microglia. It also reduced tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and IL‐6 production. This effect was correlated with the suppression of inhibitor of nuclear factor kappa B‐α (IκB‐α) phosphorylation and degradation and nuclear factor kappa B (NF‐κB) translocation and DNA binding. Additionally, KCHO‐1 upregulated HO‐1 expression by promoting nuclear translocation of nuclear factor E2‐related factor 2 (Nrf2) in mouse BV2 microglia. Tin protoporphyrin (SnPP), an HO activity inhibitor, was used to verify the inhibitory effects of KCHO‐1 on proinflammatory mediators and proteins associated with HO‐1 expression. Our data suggest that KCHO‐1 has therapeutic potential in neurodegenerative diseases caused by neuroinflammation.