Some antimethanogenic feed additives for ruminants promote rumen dihydrogen (H2) accumulation potentially affecting the optimal fermentation of diets. We hypothesised that combining an H2 acceptor with a methanogenesis inhibitor can decrease rumen H2 build-up and improve the production of metabolites that can be useful for the host ruminant. We performed three in vitro incubation experiments using rumen fluid from lactating Holstein cows: Experiment 1 examined the effect of phenolic compounds (phenol, catechol, resorcinol, hydroquinone, pyrogallol, phloroglucinol, and gallic acid) at 0, 2, 4, and 6 mM on ruminal fermentation for 24 h; Experiment 2 examined the combined effect of each phenolic compound from Experiment 1 at 6 mM with two different methanogenesis inhibitors (Asparagopsis taxiformis or 2-bromoethanesulfonate (BES)) for 24 h incubation; Experiment 3 examined the effect of a selected phenolic compound, phloroglucinol, with or without BES over a longer term using sequential incubations for seven days. Results from Experiment 1 showed that phenolic compounds, independently of the dose, did not negatively affect rumen fermentation, whereas results from Experiment 2 showed that phenolic compounds did not decrease H2 accumulation or modify CH4 production when methanogenesis was decreased by up to 75% by inhibitors. In Experiment 3, after three sequential incubations, phloroglucinol combined with BES decreased H2 accumulation by 72% and further inhibited CH4 production, compared to BES alone. Interestingly, supplementation with phloroglucinol (alone or in combination with the CH4 inhibitor) decreased CH4 production by 99% and the abundance of methanogenic archaea, with just a nominal increase in H2 accumulation. Supplementation of phloroglucinol also increased total volatile fatty acid (VFA), acetate, butyrate, and total gas production, and decreased ammonia concentration. This study indicates that some phenolic compounds, particularly phloroglucinol, which are naturally found in plants, could improve VFA production, decrease H2 accumulation and synergistically decrease CH4 production in the presence of antimethanogenic compounds.