Plantaricin is a kind of bacteriocin with broad-spectrum antibacterial activity on several food pathogens and spoilage microorganisms, showing potential in biopreservation applications. However, the low yield of plantaricin limits its industrialization. In this study, it was found that the co-culture of Wickerhamomyces anomalus Y-5 and Lactiplantibacillus paraplantarum RX-8 could enhance plantaricin production. To investigate the response of L. paraplantarum RX-8 facing W. anomalus Y-5 and understand the mechanisms activated when increasing plantaricin yield, comparative transcriptomic and proteomic analyses of L. paraplantarum RX-8 were performed in mono-culture and co-culture. The results showed that different genes and proteins in the phosphotransferase system (PTS) were improved and enhanced the uptake of certain sugars; the key enzyme activity in glycolysis was increased with the promotion of energy production; arginine biosynthesis was downregulated to increase glutamate mechanism and then promoted plantaricin yield; and the expression of several genes/proteins related to purine metabolism was downregulated and those related to pyrimidine metabolism was upregulated. Meanwhile, the increase of plantaricin synthesis by upregulation of plnABCDEF cluster expression under co-culture indicated that the PlnA-mediated quorum sensing (QS) system took part in the response mechanism of L. paraplantarum RX-8. However, the absence of AI-2 did not influence the inducing effect on plantaricin production. Mannose, galactose, and glutamate were critical metabolites and significantly simulate plantaricin production (p < 0.05). In summary, the findings provided new insights into the interaction between bacteriocin-inducing and bacteriocin-producing microorganisms, which may serve as a basis for further research into the detailed mechanism.