Acetaminophen (APAP) is the most common prescription medicine around the world for the treatment of pain and fever and is considered to be a safe drug at its therapeutic dose. However, a single overdose or frequent use of APAP can cause severe acute liver injury. APAP hepatotoxicity is a prevalent cause of acute liver disease around the world and the lack of suitable treatment makes it a serious problem. In recent years, there has been a surge in interest in using probiotics and probiotic-derived products, known as postbiotics, as health and disease negotiators. A growing body of evidence revealed that they can be equally effective against APAP hepatotoxicity. Different probiotic bacteria were found to be pre-clinically effective against APAP hepatotoxicity. Different postbiotics have also shown exciting results in preclinical models of APAP hepatotoxicity. This review summarized the protective roles and mechanisms of the different probiotic bacteria and postbiotics against APAP hepatotoxicity, with critical discussion. A brief discussion on potential novel probiotics and postbiotics for oxidative liver injury was also included. This review was written in an attempt to pique the interest of researchers in developing a safe therapeutic option against oxidative liver damage using probiotics and/or postbiotics as dietary supplements.