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We performed a proof-of-concept study to validate a peptide-conjugated peptide nucleic acid (PPNA) directed to inhibit peptidoglycan recycling as strategy to reduce AmpC hyperproduction and β-lactam resistance in Pseudomonas aeruginosa. Our nagZ-targeting PPNA at 2 µM decreased mRNA levels of nagZ and ampC to about a quarter in the AmpC high-level hyperproducer mutant PAdacBΔD and a previously characterized clinical strain with similar features, causing low cytotoxicity on human A549 cells. Ceftazidime minimum inhibitory concentration decreased from 64 to 8 mg/L in both strains after combination with 2 µM PPNA (which showed significant synergy in checkerboard assays), suggesting that nagZ-targeting PPNAs can be explored as weapons to sensitize P. aeruginosa against β-lactams and return therapeutic value to these essential drugs.