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Background: The increase of multi-resistant bacteria, especially <i>Staphylococcus</i> spp. and <i>Enterobacteriaceae</i>, constitutes a challenge in veterinary medicine. The rapid growth of resistance is outpacing antibiotic discovery. Innovative strategies are needed, including the use of natural products like <i>Allium</i> species (<i>Allium sativum</i> L. and <i>Allium cepa</i> L.), which have been used empirically for centuries to treat infectious diseases in humans and farm and aquaculture animals due to their antibacterial properties. Methods: This study aimed to evaluate the in vitro activity of two <i>Allium</i>-derived compounds, propyl propane thiosulfinate (PTS) and propyl propane thiosulfonate (PTSO), against multi-resistant <i>Staphylococcus</i> spp. (<i>n</i> = 30) and <i>Enterobacteriaceae</i> (<i>n</i> = 26) isolated from dogs referred to a veterinary teaching hospital in Madrid. Results and Discussion: The results indicated the in vitro efficacy of PTSO/PTS against the tested bacterial strains, and 56.7% of <i>Staphylococcus pseudintermedius</i> and 53.8% of <i>Enterobacteriaceae</i> showed sensitivity to PTS and PTSO compared with classic antibiotics. In addition, 50% of <i>S. pseudintermedius</i> strains resistant to erythromycin, ibofloxacin, difloxacin and orbifloxacin and 50% of <i>Enterobacteriaceae</i> strains resistant to tetracycline and doxycycline were sensitive to PTS and PTSO. Although studies are needed to verify their efficacy in vivo, the combined use of PTS and PTSO exhibits promise in enhancing bacterial sensitivity against <i>S. pseudintermedius</i> and <i>Enterobacteriaceae</i> infections, providing a first insight into the potential of both compounds in veterinary practice.