The　combined　effect　of　curcumin　and　docosahexaenoic　acid　(DHA)　on　liver　injury　has　not　yet　been　reported.　We　determined　the　synergistic　effect　of　curcumin　and　DHA　on　the　protection　of　WRL-68　cells　from　palmitic　acid-induced　injury,　and　on　the　inhibition　of　LX2　cells.　A　microemulsion　to　co-deliver　both　compounds　was　prepared　by　ultrasonic　emulsification.　Mice　were　fed　a　high-fat　diet　for　10　weeks　to　induce　mild　non-alcoholic　fatty　liver　disease　(NAFLD).　At　a　dose　of　5　mg/kg　curcumin　and　30　mg/kg　DHA,　the　microemulsion　successfully　lowered　serum　triacylglycerol　(TG)　and　low-density　lipoprotein　cholesterol　levels,　and　significantly　attenuated　NAFLD.　A　pharmacokinetic　study　in　rats　showed　that　the　microemulsion　had　a　higher　Cmax　value　for　curcumin,　a　greater　AUC0–24　value　and　a　longer　t1/2　value　for　both　curcumin　and　DHA.　This　investigation　provides　a　novel　application　of　a　combination　of　functional　food　ingredients　to　treat　chronic　liver　disease.　©　2024　The　Authors