Natural products are well known for their high potency with minimum side effects. Plant extracts are the most commonly used natural products because of their ease of availability and relatively low production cost. Berberine (BBR), a phytochemical component of some Chinese medicinal herbs (most commonlyBerberis vulgaris), is an isoquinoline alkaloid with several biological and pharmacological effects including antioxidant, anti‐inflammatory, antitumour, antimicrobial, antidepressant,hepatoprotective, hypolipidemic, and hypoglycemic actions. Interestingly, multiple studies have shown that BBR is a potential drug candidate with a multi-spectrum therapeutic application. However, the oral delivery of BBR is challenged owing to its poor bioavailability. Therefore, its oral bioavailability needs to be enhanced before it can be used in many clinical applications. This review provides an overview of the various studies that support the broad range of pharmacological activities of BBR. Also, it includes a section to address the issues and challenges related with the drug and methods to improve the properties of BBR such as solubility, stability and bioavailability that may be explored to help patients reap the maximum benefit from this potentially useful drug.