Biofilms, bacterial aggregates responsible for 80% of chronic infections, play an important role in cystic fibrosis (CF) progression. CF-associated impairments in mucociliary clearance can enable chronic biofilm growth, leading to lung scarring and respiratory failure. Current treatments are nephrotoxic and ineffective. This research investigated the anti-biofilm potential of salicylate derivatives, a class of benzoic acids selected for their potential to inhibit bacterial adhesion, quorum sensing, and cell motility. The efficacy of three salicylates (acetylsalicylic acid, salicylic acid, and sodium salicylate) was tested alone and in combination with relevant antibiotics (tobramycin, ciprofloxacin, vancomycin) against Pseudomonas aeruginosa (PA14) and methicillin-sensitive Staphylococcus aureus (MSSA) biofilms. Salicylates outperformed antibiotics, with salicylic acid eradicating 98.7% of PA14 biomass at 1 µg/mL. Synergistic behaviour was also exhibited, increasing MSSA eradication by 21%. To verify statistical significance, normally-distributed samples underwent an unpaired two-tailed T-test, yielding p-values below an adjusted significance threshold. Non-normally distributed samples underwent non-linear curve regression and an extra-sum of squares F-test; these also verified significance. Salicylates represent a promising, non-toxic, and cost-effective treatment for CF biofilms. They can be applied via intravenous, oral, or nebulized delivery, making them a valuable candidate for future CF therapies.