Our objective was to investigate the impact of methionine supply during late-gestation on metabolism and DNA methylation in bovine placenta from cows carrying male or female calves. Multiparous cows were fed during the last 28 d of pregnancy a control diet or the control plus rumen-protected methionine (MET; Mepron, Evonik Nutrition & Care GmbH; 0.09% of DMI) to achieve a 2.8:1 ratio of Lys:Met in the metabolizable protein. Placentome samples were collected from 15 cows/treatment and organized according to diet and offspring sex as follows: Male CTR (n = 7), Male MET (n = 7), Female CTR (n = 8), and Female MET (n = 8). Targeted metabolomics (LC-MS), RT-PCR, Western blotting, and enzyme activity were performed to quantify metabolic activity through the TCA cycle, 1-carbon metabolism, transsulfuration, and global DNA methylation. Compared with cows carrying Male CTR, cows carrying Male MET delivered heavier calves. Compared with placenta from Male CTR, Male MET placenta had greater concentrations of metabolites in the TCA cycle (isocitric acid and NADH) and transsulfuration pathway (cysteinesulfinic acid, glutathione and vitamin B₁₂). Male MET placenta had greater methionine synthase (MTR) activity than Male CTR, while betaine-homocysteine S-methyltransferase (BHMT) and cystathionine-β-synthase (CBS) were not affected. No differences in global DNA methylation or mRNA and protein expression of the DNA methyl transferases were observed between Male CTR and Male MET. Cows carrying Female CTR and Female MET delivered calves with similar body weight at birth. Female MET compared with Female CTR placenta had greater concentrations of metabolites related to 1-carbon metabolism (Met and S-adenosyl-methionine). Enzyme activities in female placenta were not affected by methionine supply. The mRNA and protein expression of DNMT3A and DNMT3B was greater in Female MET than Female CTR, while DNMT1 was not affected by MET supply. Global DNA methylation was lower in Female MET than Female CTR placenta. Overall, our findings suggest that diet affects placental metabolism and DNA methylation and also highlight the importance of studying sex-specific responses to dietary interventions.