Some antibiotics have lost their efficacy over common infections and this has led to the search for new antibiotics and chemically altering existing ones for a better control of infectious diseases. In the present study, Pyrenacantha grandiflora tubers extracts were conjugated with ampicillin, penicillin, vancomycin and silver nanoparticles and their antimicrobial activity was evaluated against Escherichia coli, Staphylococcus aureus and Klebsiella Pneumoniae. The reactions were confirmed by formation of new functional groups that were identified by Fourier transmission infrared spectroscopy (FTIR). Minimum inhibitory concentrations were determined using the microdilution assay. Minimum bactericidal concentrations and the fractional inhibition concentration index were also determined. FTIR analysis indicated different functional group associated with conjugation. The activity of ampicillin was improved when conjugated with silver nanoparticles against K. pneumonia and E. coli. Vancomycin showed improvement of activity when conjugated to silver nanoparticles against K. pneumonia. Penicillin was improved by acetone extracts and vancomycin showed to be more effective when conjugated with silver nanoparticles and water extracts. The conjugation of P. grandiflora with penicillin, ampicillin and vancomycin in the presence of silver nanoparticles improved their biological activities. Therefore, the conjugates are medicinally important and can be used to improve the activity of existing antibiotics.