Peripartal dairy cows undergo a period of low methionine (MET) and choline (CHOL) supply, hence, rumen-protected MET or CHOL feeding may improve performance and cow health at least in part via alterations of the tissue metabolome. Objectives were to investigate the effect of feeding rumen protected MET (Smartamine M) or rumen protected CHOL (Reashure) during the peripartal period on liver metabolomics profile and identify most-impacted metabolites using a high-resolution mass spectrometry untargeted approach. Twenty-four multiparous Holstein cows were randomly assigned from −21 to +30 d relative to parturition to a basal control (CON) diet; CON plus rumen-protected methionine (MET) at a rate of 0.08% of DM; or CON plus rumen-protected choline (CHOL) at 60 g/d. Liver samples were harvested at −10, 7, and 20 d. Samples were analyzed using the Q-Exactive MS system after LC (Liquid chromatography) separation. Data analysis was performed using the MetaboAnalyst 3.0 program. A total of 3346 metabolites were identified. Multivariate statistical analysis (PLS-DA, and OPLS-DA) revealed clear separation of metabolite profile among CON, MET, and CHOL groups at −10, 7, and 20 d. Metabolites with ‘importance in projection (VIP)’ scores >1.0 and P < 0.05 were considered significantly different among treatments. The top 15 metabolites with highest VIP score were identified by exact molecular weight (mass error ppm <5) for comparisons at −10 d, 7 d, and 20 d, respectively. Among significant metabolites at −10 d, dityrosine (an oxidative stress biomarker, VIP = 3.6) and norophthalmic acid (a glutathione analog, VIP = 2.9) levels were greater in CHOL-fed cows but lower in MET-fed cows. In contrast, ophthalmic acid (another glutathione analog, VIP = 3.7) at 20 d was greater in MET-fed cows but lower in CHOL-fed cows compared with CON. At 7 d, hepatic dimethylglycine was greater (VIP = 2.6) in CHOL cows but lower in MET-fed cows compared with CON. These analyses indicate that peripartal MET or CHOL feeding can influence the liver metabolome to different extents. The biologic significance of these alterations remains to be elucidated.