Antimicrobial resistance (AMR) is a major threat to global public health. Medicinal plants have long been used as remedies for infectious diseases by native cultures around the world and have the potential for providing effective treatments for antibiotic-resistant infections. Rhamnus californica (Rhamnaceae) and Umbellularia californica (Lauraceae) are two indigenous California plant species historically used by Native Americans to treat skin, respiratory and gastrointestinal infections. This study aimed to assess the in vitro antimicrobial activity of methanolic extracts of leaves and bark of R. and U. californica against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive and Gram-negative bacteria. Methanolic extracts of leaves and bark of R. and U. californica were prepared by soxhlet extraction and evaluated for their antimicrobial activity against Bacillus cereus, Streptococcus pyogenes, Mycobacterium smegmatis, Staphylococcus aureus, MRSA, Escherichia coli and Pseudomonas aeruginosa using disc diffusion and minimal inhibitory concentration (MIC) assays. Chemical profiling of the extracts was performed using standard methods. All extracts inhibited the growth of MRSA and other Gram-positive bacteria with MICs of 3.3-6.0 mg/ml. Gram-negative organisms were unaffected by these extracts. U. californica extracts (leaves and bark) had the lowest MIC values. Chemical profiling detected the presence of quinones, alkaloids, flavonoids, cardenolides, tannins and saponins in these extracts. Our study is the first to report the antimicrobial properties of R. and U. californica and illustrates their promising anti-MRSA potential. Our results give scientific credence to the traditional medicinal uses of these plants by the indigenous peoples of California. Further investigation of the secondary metabolites responsible for the antimicrobial activity of these extracts against MRSA is warranted.