| Summary: | The calyxes and fruits of <i>Physalis alkekengi</i> L. var. <i>franchetii</i> (Mast.) Makino (<i>P. alkekengi</i>), a medicinal and edible plant, are frequently used as heat-clearing and detoxifying agents in thousands of Chinese medicine prescriptions. For thousands of years in China, they have been widely used in clinical practice to treat throat disease, hepatitis, and bacillary dysentery. This systematic review summarizes their structural analysis, quality control, pharmacology, and pharmacokinetics. Furthermore, the possible development trends and perspectives for future research studies on this medicinal plant are discussed. Relevant information on the calyxes and fruits of <i>P. alkekengi</i> was collected from electronic databases, Chinese herbal classics, and <i>Chinese Pharmacopoeia</i>. Moreover, information was collected from ancient documents in China. The components isolated and identified in <i>P. alkekengi</i> include steroids, flavonoids, phenylpropanoids, alkaloids, nucleosides, terpenoids, megastigmane, aliphatic derivatives, organic acids, coumarins, and sucrose esters. Steroids, particularly physalins and flavonoids, are the major characteristic and bioactive ingredients in <i>P. alkekengi</i>. According to the literature, physalins are synthesized by the mevalonate and 2-C-methyl-<span style="font-variant: small-caps;">d</span>-erythritol-4-phosphate pathways, and flavonoids are synthesized by the phenylpropanoid pathway. Since the chemical components and pharmacological effects of <i>P. alkekengi</i> are complex and varied, there are different standards for the evaluation of its quality and efficacy. In most cases, the analysis was performed using high-performance liquid chromatography coupled with ultraviolet detection. A pharmacological study showed that the crude extracts and isolated compounds from <i>P. alkekengi</i> had extensive in vitro and in vivo biological activities (e.g., anti-inflammatory, anti-tumor, immunosuppressive, antibacterial, anti-leishmanial, anti-asthmatic, anti-diabetic, anti-oxidative, anti-malarial, anti-Alzheimer’s disease, and vasodilatory). Moreover, the relevant anti-inflammatory and anti-tumor mechanisms were elucidated. The reported activities indicate the great pharmacological potential of <i>P. alkekengi</i>. Similarly, studies on the pharmacokinetics of specific compounds will also contribute to the progress of clinical research in this setting.
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