Tea polyphenols are non-toxic plant extracts. However, tea polyphenols' impact on antibiotic tolerance development in the environment remains uncertain. In this study, where Escherichiacoli K12 was exposed to tetracycline as a stressor, tea polyphenols were applied for 31 days to induce a tolerant phenotype. Transcriptomics analyses and flow cytometry were used to study the mechanisms. In simple terms, tea polyphenols can delay the onset of tolerance by decreasing cellular metabolism including (ATP synthetics, citrate cycle, and sulfur metabolism), reducing amino acid synthesis (such as methionine, cysteine, glycine, serine, and threonine metabolism), oxidizing external cellular structures, especially peptidoglycan and preventing cells into a dormant state. This sheds light on how natural polyphenolic substances have evolved to mitigate tolerance.