Here, two new topical hydrogel formulations (R1HG-3c and R1HG-4b), promising to treat staphylococcal skin infections, have been developed. To this end, two pyrazoles (3c and 4b) previously reported to possess antibacterial activity against multi drug resistant (MDR) staphylococci, were used as active ingredients, while a polystyrene-based cationic resin (R1) was employed as gelling agent. Particularly, we synthesized and characterized R1, which showed high hydrophilicity, high-level porosity, excellent swelling capabilities, and aptitude to form hydrogel by simple dispersion in water, thus allowing to formulate 3c and 4b as hydrogels, without using any further additive. The obtained R1HG-3c and R1HG-4b showed high equilibrium degrees of swelling (EDS) of 765% and 675%, as well as great equilibrium water contents (EWC) of 88% and 87%, respectively. Chemometric-assisted attenuated total reflectance (ATR) Fourier transform infrared (FTIR) analyses, as well as optical and scanning electronic microscopy were employed to investigate the chemical structure and morphology of both soaked and dried hydrogels. Weight loss studies helped in assessing the water release profiles of hydrogels, whose stability over 4 months was inspected by monitoring their inversion properties and by chemometric-assisted ATR-FTIR spectroscopy. By proper experiments, including amplitude and frequency sweep studies, the flow and dynamic rheological behaviour of the gels was evaluated. Finally, their content in NH₃⁺ groups deriving from R1, and known to promote the antibacterial effects, was determined by potentiometric titrations. Collectively, the favourable physicochemical characteristic of R1HG-3c and R1HG-4b, as well as the demonstrated antibacterial effects of their ingredients (3c and 4b) against MDR staphylococci, possibly further improved by the cationic R1, support the future development of our pyrazole-enriched hydrogels as new weapons to treat severe skin and wound infections sustained by MDR bacteria of Staphylococcus genus.