Blackcurrant is rich in polyphenolic substances with corresponding antioxidant and anti-inflammatory properties. Therefore, based on the identification of typical functional components of blackcurrant polyphenols (BCP), the present study investigated the therapeutic effects of BCP on alcoholic liver disease (ALD) by modulating fibroblast growth factor 21 (FGF21) in both an in vitro HepG2 cell model and an in vivo C57BL/6J mouse model of acute alcoholism. In total, 892 polyphenols and 45 anthocyanins were identified in blackcurrant. Among them, 6 anthocyanins were identified in blackcurrant for the first time. In addition, alcohol induces FGF21 signalling from the liver to the brain, where it exerts a detoxifying effect by activating the noradrenergic nervous system, which regulates arousal and alertness. It has been experimentally demonstrated that BCP promotes the expression of FGF21, thereby alleviating acute alcoholism through the pathway of the liver–brain axis. Besides, BCP attenuates ALD through antioxidant and anti-inflammatory effects. The results indicate that BCP can protect the liver and also provide insights into developing and utilizing blackcurrant in the treatment of ALD.