Abstract The objective of the present study was to evaluate the antimicrobial potential of Artocarpus heterophyllus dry leaves extracts on S. enterica and E. coli and their interaction with conventional antimicrobials. Dried powdered leaves were used to produce hexane (Hex), methanolic (MeOH) and ethanolic residue (EtOHr) extracts. The antimicrobial test was performed against Escherichia coli, ATCC 25922, E. coli EPEC, CDC 086H35, and Salmonella enterica serotype Enteritidis phagotype 4 (SE PT4) through minimal inhibition concentration (MIC) and minimal bactericidal concentration (MBC). The agar diffusion technique, well and disc-variants were used to measure the antimicrobial effect of the plant extract combination with antimicrobial of clinical usage. We highlight the bactericidal effect of jackfruit tree leaves on E. coli and S. enterica SE PT4 at 7.2 mg/mL and the effect of the extracts on antimicrobial activity. The interaction between chloramphenicol and dry leaves extracts was characterized by both synergism and antagonism depending on extract type and bacteria used. The interaction between antimicrobial of clinical usage and jackfruit tree leaves extracts demonstrated changes in susceptibility profile of antimicrobials tending to an antagonist effect. As the jackfruit tree leaves may interfere on antimicrobials action, special attention should be given to its usage as traditional medicine in the treatment of food borne diseases.