This study aimed to investigate the effects of Plantago ovata plant extract on the expression of beta-lactamase-producing genes in multidrug-resistant (MDR) K. pneumoniae isolates. This study was conducted on 50 samples of COVID-19 patients admitted to the intensive care unit of respiratory hospitals. K. pneumoniae isolates were identified using standard biochemical tests, culturing, and Gram staining. The antibiotic susceptibility profile of isolates was determined using the micro broth dilution method. Then, P. ovata extract was prepared and its effects on the expression of MDR K. pneumoniae genes were evaluated. Totally, 50 samples were collected from 50 patients (25 males and 25 females, 58 ± 2.2 years of age) with COVID-19 infection. Thirty K. pneumoniae strains, 4 K. oxytoca strains, 2 K. mobilis strains, and 2 strains of K. rhinoscleromatis were isolated here. Gentamicin and chloramphenicol did not affect the strains and piperacillin/tazobactam was the most effective antibiotic. CTX-M15, OXA-48, and OXA-181 genes were detected in 29 (96.6%), one (1.66%), and one (1.66%) K. pneumoniae strains, respectively. The minimum inhibitory concentration of P. Ovata was 3.125 μg/ml for the isolated bacteria, and the extract significantly downregulated OXA-48 and OXA-181 genes (p<0.005, CI=95%). P. ovata extract showed antibacterial effects on MDR species of clinically isolated K. pneomoniae. Downregulation of beta-lactamase enzyme-producing genes can be considered as the possible mechanism action of antibacterial effects of the plant.