The decline in antibiotic discoveries and the rise in antibiotic resistance have rendered many antibiotics ineffective against bacterial infections. To address this challenge, researchers are exploring combinatorial therapies that blend medicinal plants with conventional antibiotics, potentially revitalizing existing drugs against antibiotic-resistant bacteria. Native South African plants including Terminalia gazensis Bak. f., Terminalia prunioides Laws. and Terminalia sericea Burch. ex D.C., have documented antimicrobial properties. However, the potential of combinations of these extracts and conventional antibiotics remains unexplored against β-lactam resistant pathogens. In this study, leaves collected from selected Terminalia spp. were extracted using varying polarity solvents, and the antibacterial activities of the extracts evaluated using disc diffusion (agar) and liquid micro-dilution (LD) assays. The toxicity of the extracts was assessed using Artemia franciscana nauplii (brine shrimp larvae) lethality (ALA) assays. With the exception of the T. sericea water extract, all exhibited mild to moderate antibacterial activities against β-lactam-sensitive and β-lactam-resistant pathogens in liquid microdilution assays. The T. gazensis methanol extract demonstrated noteworthy activity against the S. aureus and MRSA pathogen pair (LD MIC = 862.5 µg/mL), while the T. prunioides methanol extract was most effective against the antibiotic-sensitive K. pneumoniae strain (MIC = 1325 µg/mL). Notably, synergistic effects were observed in twenty-five extract/antibiotic combinations, whilst nineteen combinations displayed additive effects, sixteen were non-interaction and nineteen were antagonistic. Most of the combinations containing gentamicin resulted in antagonistic interactions. Further investigation is required in order to identify the active components and mechanisms of action underlying these synergies, which offer potential pathways for the development of more effective antibiotic treatments against antibiotic-resistant bacteria.