Resistance to antimicrobial drugs as a result of prolonged use usually results in clinical failure, especially in wound infections. Development of effective antimicrobial therapeutics for the management of infected wounds from a natural source with improved therapeutic effects is a pressing need. In this study, carbopol-mastic gum-based topical gels were loaded with silver nanoparticles in combination with either neem bark extract or carvacrol oil. The effect of combining silver nanoparticles with neem bark extract or the essential oil carvacrol in the prepared gel formulations was investigated on selected bacterial strains. The prepared gels were characterised by Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM) and ultraviolet-visible (UV-vis) spectroscopy, followed by antimicrobial analysis against selected strains of bacteria. There was no interaction between the loaded natural extract or essential oil and the polymer used for the preparation of the formulations, which was visible from the FTIR spectra of the formulations. The gels were selective and effective against selected strains of bacteria. However, the combination of the silver nanoparticles with essential oil or natural extract in some of the gel formulations rendered the formulation ineffective against some of the bacterial strains. The gel formulations were effective against bacterial strains such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis which are the common causes of wound infections. Incorporation of silver nanoparticles into the topical formulations with natural extracts is usually a good approach to overcome antibiotic-resistant infections. However, the combination of antibacterial agents must be managed carefully.