Aims: The study was aimed to explore the antimicrobial potential of ethanolic leaf extracts of Eucalyptus globulus, Moringa oliefera, Syzygium cumini and Citrus limon against antibiotic-resistant Clostridium perfringens type D (n=5). Methodology and results: Antibiotic resistance pattern of C. perfringens type D isolates against tetracycline, gentamicin, ceftriaxone, amoxicillin and streptomycin was evaluated by disc diffusion method. Well diffusion and micro broth dilution methods were used to determine the anti-bacterial activity, sub-inhibitory concentrations and antibiotic resistance modulating effects of the plant extracts. Ethanolic extract of E. globules was selected to evaluate its modulatory impact and subjected to GC-MS analysis to separate and identify the phytochemicals. The results showed that the isolates were resistant to gentamicin (0 ± 0.00 mm), streptomycin (0 ± 0.00 mm), tetracycline (13.2 ± 2.28 mm) and ceftriaxone (0 ± 0.00 mm) while sensitive to amoxicillin (23.8 ± 1.30 mm) and tetracycline (13.2 ± 2.28 mm). Eucalyptus globulus exhibited the maximum anti-bacterial activity with a zone of inhibition (ZOI) of 14.6 ± 0.54 mm and minimum inhibitory concentration (MIC) (1500 ± 947.85 µg/mL). Other plant extracts (M. oliefera, S. cumini and C. limon) also showed anti-bacterial activity but couldn’t modulate the resistance. The activity of ceftriaxone associated with E. globulus extract was improved with 20.2 ± 0.20 mm ZOI at 78.125 µg/mL sub-inhibitory concentration. Conclusion, significance and impact of study: The study results indicate the possible use of the ethanolic extract of E. globulus alone or in combination with common antibiotics for the treatment of C. perfringens infections in small ruminants.