Staphylococcus aureus(S. aureus) skin infections remain a prevalent public health concern worldwide, posing ongoing challenges in treatment.Uvaria chamaeroots has demonstrated significant effectiveness againstS. aureus. This study aimed to propose a dermal formulation based onUvaria chamaefor treating bacterial skin infections. The antibacterial activity was first confirmed. Tests including the time-kill test, the erythromycin outer membrane permeability test, and the ATPase/H+ proton pump inhibition test were conducted to explore the antibacterial mode of action. A cream was prepared using the phase inversion technique and subjected to quality control and senso-rheological testing. The cream was tested for antibacterial activity and skin toxicity (OECD guideline 404). Thein vivoantibacterial effect and wound-healing potential of theUvaria chamaecream were then assessed on Wistar rat. The ethanolic extract ofUvaria chamaeroot exhibited bactericidal effects on the testedS. aureusstrains. In combination with erythromycin, the extract enhanced the permeability ofS. aureus’s outer membrane while inhibiting ATPase/H+ proton pumps. The pharmaceutical quality of the produced cream revealed acceptable macroscopic conditions and satisfactory homogeneity. Antibacterial activity evaluation showed significant activity at low concentrations. The cream’s healing properties indicated a significant decrease in wound diameter (p<0.05) over time, culminating in complete healing on day 13 for the treated group, with a retraction percentage of 99.99%. These findings support the safe use ofUvaria chamaeextracts in managingS. aureusskin infections and pave the way for pre-clinical testing and potential market introduction of this cream.