The study investigates the mechanisms underlying antibiotic tolerance in nutrient-limited and biofilm-growing *Pseudomonas aeruginosa*. It demonstrates that this tolerance is mediated by active starvation responses rather than passive growth arrest. The protective mechanism is controlled by the stringent response (SR), which reduces oxidant stress in bacterial cells. Disrupting the SR in *P. aeruginosa* increased the sensitivity of biofilms to four different classes of antibiotics and enhanced the efficacy of antibiotic treatment in experimental infections. The SR mediates this tolerance by curbing the production of pro-oxidant metabolites and enhancing antioxidant defenses. These findings suggest that targeting these physiological adaptations could improve the effectiveness of existing antibiotics and address the growing problem of antibiotic resistance.The study investigates the mechanisms underlying antibiotic tolerance in nutrient-limited and biofilm-growing *Pseudomonas aeruginosa*. It demonstrates that this tolerance is mediated by active starvation responses rather than passive growth arrest. The protective mechanism is controlled by the stringent response (SR), which reduces oxidant stress in bacterial cells. Disrupting the SR in *P. aeruginosa* increased the sensitivity of biofilms to four different classes of antibiotics and enhanced the efficacy of antibiotic treatment in experimental infections. The SR mediates this tolerance by curbing the production of pro-oxidant metabolites and enhancing antioxidant defenses. These findings suggest that targeting these physiological adaptations could improve the effectiveness of existing antibiotics and address the growing problem of antibiotic resistance.