BACKGROUND The evolution of resistance to antimicrobials is a ubiquitous phenomenon. The evolution of antibiotic resistance in Staphylococcus aureus suggests that there is no remedy with sustaining effectiveness against this pathogen. The limited number of antibacterial drug classes and the common occurrence of cross-resistant bacteria reinforce the urgent need to discover new compounds targeting novel cellular functions. Natural products are a potential source of novel antibacterial agents. Anti-MRSA (methicillin-resistant S. aureus) bioactive compounds from Streptomyces and the anti-MRSA activity of a series of plant extracts have been reviewed respectively. However, there has been no detailed review of the precise bioactive components from plants. OBJECTIVE The present review aimed to summarize the phytochemicals that have been reported with anti-MRSA activities, analyze their structure-activity relationship and novel anti-MRSA mechanisms. METHODS Data contained in this review article are compiled from the authoritative databases PubMed, Web of Science, Google Scholar, and so on. RESULTS This review summarizes 100 phytochemicals (27 flavonoids, 23 alkaloids, 17 terpenes and 33 others) that have been tested for their anti-MRSA activity. Among these phytochemicals, 39 compounds showed remarkable anti-MRSA activity with MIC values less than 10 μg/ml, 14 compounds with MIC ranges including values < 10 μg/ml, 5 compounds with MIC values less than 5 μM; 11 phytochemicals show synergism anti-MRSA effects in combination with antibiotics. Phytochemicals exerted anti-MRSA activities mainly by destroying the membrane structure and inhibiting the efflux pump. CONCLUSIONS The 58 compounds with excellent anti-MRSA activity the 11 compounds with synergistic anti-MRSA effect, especially cannabinoids, xanthones and fatty acids should be further studied in vitro. Novel targets, such as cell membrane and efflux pump could be promising alternatives to develop antibacterial drugs in the future in order to prevent drug resistance.