This study was performed to assess the potential β-lactamase inhibitory properties of nineteen crude Saudi plant extracts belonging to eight families against extended spectrum β-lactamase (ESβL) strains of Klebsiella pneumoniae and other medically important pathogens. A total of 276 microbial isolates of pathogenic bacteria were used in this study; only 15 of them showed decreased sensitivity to one or several of ceftazidime, aztreonam, cefotaxime or ceftriaxone, which are deemed to be possible producers of ESβL. Antibacterial activities of plant extracts were carried out against ESβL positive isolates by the disc diffusion method. The potential ESβL suppressing activities of plant extracts and prepared fractions, (chloroform and methanol), with or without antibiotic were studied by disc diffusion method. Results revealed that selected plant extracts showed no antibacterial activity against tested strains; meanwhile, only Echinops viscosus, Pulicaria arabica, Tephrosia nubica, Chrozophora oblongifolia, and Clutia myricoides showed pronounced ESβL inhibitory activities. The extracts were quantified for phenolic compounds and their antioxidant properties. Bio-guided fractionation of the active extracts revealed that the chloroform fraction of C. myricoides possess a promising ESβL inhibitory activity. The separation and the structural elucidation of the active compounds from C. myricoides will offer beneficial leads for developing β-lactamase inhibitors.