This study included three experiments using a semi-automated in vitro gas production technique to investigate the potential of resveratrol (RES) and curcumin (CUR) as natural alternatives to monensin (MON) for preventing ruminal acidosis. In Experiment 1, different concentrations (100, 200, and 400 µg/mL) of RES, CUR, a combination of both (MIX), MON (12 µg/mL), and a control group were evaluated for their ability to counteract ruminal acidosis. Acidosis was induced by incubating glucose (0.1 g/mL) without buffer for 6 h to simulate a highly fermentable, unbuffered ruminal environment. In Experiment 2, RES (200 µg/mL), CUR (200 µg/mL), MIX (200 µg/mL), and MON were compared when buffer was added, and fermentation was extended to 24 h using the same substrate as in Experiment 1. Experiment 3 examined the effect of RES (200 µg/mL) on acidosis in vitro using corn, barley, or wheat as substrates, and compared it to MON. In Experiment 1, pH increased significantly (P < 0.05) and gas production decreased (P < 0.01) with the addition of RES and MIX at 200 and 400 g/mL as well as MON at 12 µg/mL, whereas CUR had no effect on pH (P > 0.05). In Experiment 2, both RES and MON increased pH (P < 0.01) and reduced (P < 0.01) lactic acid concentration. MON and RES increased (P < 0.01) propionic acid and reduced (P < 0.01) the acetate to propionate ratio. While MON significantly reduced total volatile fatty acid (VFA) concentrations (P < 0.01) compared to the control, RES had no significant effect. In Experiment 3, when corn was used as a substrate, RES was found to significantly increase (P < 0.01) pH and decrease lactic acid levels in comparison to barley or wheat. MON improved (P < 0.01) propionate levels and decreased (P < 0.01) the ratio of acetate to propionate. Both RES and MON did not affect the total VFA. In conclusion, RES shows promise as a natural alternative to MON for preventing rumen acidosis, particularly when corn is used as a basal diet. The findings indicate that RES can effectively increase ruminal pH and reduce lactic acid levels, which are key factors in mitigating acidosis.