Lactiplantibacillusplantarum is a species of lactic acid bacteria (LAB) commonly used in food. However, before it is used in food, the safety evaluation of antibiotic resistance must be carried out. Our study found that L.plantarum FZJTZ19M1 and FZJTZ29M8 had a high tetracycline resistance phenotype, but they did not contain any known tetracycline resistance genes. To investigate the tetracycline resistance mechanism of these two strains, we used transcriptome technology to explore the differentially expressed genes (DEG) produced by these two strains after tetracycline induction. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were used to reveal the important functional genes. Transcriptome results showed that 234 and 176 DEG were identified in L.plantarum FZJTZ19M1 and FZJTZ29M8, respectively. The results of GO, KEGG enrichment analysis, and PPI network analysis suggested that the resistance of L.plantarum FZJTZ19M1 to tetracycline might be caused by regulating amino acid metabolism and reducing the metabolism of fatty acids, biotin, and other substances. L.plantarum FZJTZ29M8 may increase resistance to tetracycline mainly by using (ATP-binding cassette) ABC transporters to excrete tetracycline from the body and reducing its cellular metabolism. This study revealed the tetracycline resistance mechanism of two L.plantarum strains at the transcriptional level and provided the theoretical reference for the safe application of this kind of LAB in food.