BACKGROUND: This study focuses on the investigation of the antioxidant and anti-inflammatory activities of alcohol extracts from Ribes nigrum leaves on murine BV-2 microglial Wt and Acyl-CoA oxidase 1 deficient (Acox1 METHODS: The extract chemical composition was analyzed via LC-Q-Orbitrap HRMS. Various assays, including DPPH, MTT, and H RESULTS: Investigations showed the presence of phenolic compounds in this extract, among which flavan-3-ols, flavonols, furanocoumarins, hydroxycinnamates were major components, which are known for their biological activity in various test systems. The MTT test revealed a concentration of 0.125 mg/mL of R. nigrum extract as the highest non-toxic. The investigated extract showed high antioxidant activity in chemical-based tests. The antioxidant potential of the R. nigrum leaf extract was furtherly explored using the BV-2 microglial cell line models. Moreover, the extract was found to alter the activity of the main antioxidant enzyme, catalase and fatty acid oxidation enzyme, Acyl-CoA oxidase 1 (ACOX1) as well as the expression of appropriate genes in Wt and Acox1 CONCLUSION: Our study demonstrated the protective effects of R. nigrum leaf extracts on BV-2 microglial cells by reducing oxidative and nitrosative stress, decreasing pro-inflammatory gene expression, and normalizing peroxisomal function, highlighting the potential of these extracts as therapeutic agents for managing oxidative stress and inflammation.