There were several reports on the isolation of sinensetin from O. reticulate are recognized as food supplements and nutrition while their leaf extracts and essential oils have shown strong pharmacological activities such as antimicrobial ( Tao et al., 2014), anti-inflammatory ( Nasri et al., 2017), antioxidant ( Nasri et al., 2017), anticancer ( Benavente-Garcia O and Castillo, 2008), antiproliferative ( Du, and Chen, 2010), hypoglycemic ( Aruoma et al., 2012) and analgesic effects ( Nasri et al., 2017). Moreover, many Citrus species among the different variety of C. For instance, fruit peels of Citrus reticulata Blanco have been used in Asian ethnomedicine to treat indigestion, bronchial, fever, snakebite, stomachache, edema, cardiac diseases, bronchitis and asthmatic conditions ( Kang et al., 2013). Many citrus fruits have been used traditionally for many medicinal purposes. aristatus have been shown to exhibit excellent pharmacological activities such as antioxidant ( Awale et al., 2003), antibacterial ( Ho et al., 2014), hepatoprotective ( Yam et al., 2007), anti-inflammatory ( Hsu et al., 2010), cytotoxic ( Yam et al., 2007), antihypertensive ( Azizan et al., 2012) and gastroprotective ( Yam et al., 2009). Orthosiphon aristatus is widely employed in traditional medicine as a diuretic ( Beaux et al., 1999 Adam et al., 2009) and to treat hypertension ( Mohamed et al., 2012 Manshor et al., 2013), rheumatism, tonsillitis, gout, menstrual disorder and diabetes ( Adam et al., 2009 Mohamed et al., 2012). In this review, an insight on sinensetin pharmacological activities and mechanisms of action serves as a useful resource for a more thorough and comprehensive understanding of sinensetin as a potential lead candidate for drug discovery. More in vivo studies in various animal models including toxicity, pharmacokinetic, pharmacodynamic and bioavailability studies are required to assess its efficacy and safety before submission to clinical studies. However, more detail mechanistic studies are needed to understand its pharmacological effects. The studies provided some insights on its several mechanisms of action in cancer and other disease states. In-vitro and in-vivo studies showed that sinensetin possessed strong anticancer activities and a wide range of pharmacological activities such as anti-inflammatory, antioxidant, antimicrobial, anti-obesity, anti-dementia and vasorelaxant activities. The databases employed for data collection are mainly through Google Scholar, PubMed, Scopus and Science Direct. The present findings about the compound are critically analyzed and its prospect as a lead molecule for drug discovery is highlighted. This review aims to compile an up-to-date reports of published scientific information on sinensetin pharmacological activities, mechanisms of action and toxicity. aristatus and several citrus fruits, has been found to possess strong anticancer activities and a variety of other pharmacological benefits and promising potency in intended activities with minimal toxicity. Sinensetin, a plant-derived polymethoxylated flavonoid found in Orthosiphon aristatus var. 2Institute of Systems Biology, Universiti Kebangsaan Malaysia, Bangi, Malaysia.1Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.Lee Han Jie 1, Ibrahim Jantan 2, Syaratul Dalina Yusoff 1, Juriyati Jalil 1 and Khairana Husain 1*