The food fermentation performed by Saccharomyces cerevisiae sometimes needs the co-existence of or is occasionally contaminated by other microorganisms. Among these microorganisms, the co-existed lactic acid bacteria (LAB) could inhibit S. cerevisiae growth through secreting organic acids and competing for viable space and nutrients. However, besides these three known major inhibition factors, are there any other unknown influence(s) of LAB on S. cerevisiae? In this study, a “reeling-off”-based design was performed to discover the potential novel LAB co-existence-associated inhibition factor(s) on S. cerevisiae fermentation performance illustrated by the case of Lactobacillus plantarum. After excluding the previously reported major influence factors one by one, L. plantarum ATCC8014 could still inhibit yeast biomass. Such results suggested that there might really exist such previously un-detected factor(s) functioning in inhibiting yeast cell growth. Furthermore, it was discovered that the L. plantarum cell wall could inhibit S. cerevisiae growth through direct contact. Interestingly, such direct contact could also improve ethanol tolerance of S. cerevisiae and ethanol production efficiency per OD. These results would strengthen our understanding of microbial interactions during food fermentation.