The present disclosure relates generally to a pharmaceutical compositions and methods of reducing acetaminophen-induced liver toxicity. The disclosure includes pharmaceutical compositions including acetaminophen and one or more components selected from S-adenosylhomocysteine (SAH), S-methylmethionine (SMM), or a pharmaceutically acceptable salt thereof. The disclosure also relates to methods of reducing acetaminophen-induced liver toxicity in a subject by administering or co-administering one or more of S-adenosylhomocysteine (SAH), S-methylmethionine (SMM), or a pharmaceutically acceptable salt thereof, with acetaminophen to a subject.