Saccharomyces cerevisiae is the primary microorganism involved in ethanol production. Nonetheless, the buildup of ethanol inhibits yeast cell proliferation, consequently diminishing ethanol production. In this study, we applied histidine-modified Fe3O4 nanoparticles (His-Fe3O4) for the first time, to the best of our knowledge, as a means of enhancing ethanol yield during the S. cerevisiae fermentation process. The results demonstrated that exposing S. cerevisiae cells to Fe3O4 nanoparticles (Fe3O4 NPs) led to increased cell proliferation and glucose consumption. Furthermore, the introduction of His-Fe3O4 significantly boosted ethanol content by 17.3% (p < 0.05) during fermentation. Subsequent findings indicated that the rise in ethanol content correlated with enhanced ethanol tolerance and improved efficiency of electron transport. This study verified the favorable impacts of His-Fe3O4 on S. cerevisiae cells and proposed a versatile, straightforward approach for enhancing ethanol production in S. cerevisiae fermentation. This enhancement is achieved through the mediation of improved ethanol tolerance, promising substantial potential in the fermentation and bioenergy sector.