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Plants of genus Celastrus (Celastraceae) have been widely used in traditional Chinese medicine (TCM) and Indian medicine to treat cognitive dysfunction, epilepsy, insomnia, rheumatism, gout, and dyspepsia for thousands of years. We critically summarized the current evidence on the botanic characterization and distribution, ethnopharmacology, secondary metabolites, pharmacological activities, qualitative and quantitative analysis, and toxicology of Celastrus species to provide perspectives for developing more attractive pharmaceuticals of plant origin. The relevant information on Celastrus species was gathered from worldwide accepted scientific databases via electronic search (Web of Science, SciFinder, PubMed, Elsevier, SpringerLink, Wiley Online, China Knowledge Resource Integrated, and Google Scholar). Information was also obtained from the literature and books as well as PhD and MSc dissertations. Plant names were validated by "The Plant List" (www.theplantlist.org). Comprehensive analysis of the above mentioned databases and other sources confirmed that ethnomedical uses of plants of Celastrus genus had been recorded in China, India, and other countries in Southern Asia. The phytochemical investigation revealed the presence of β -dihydroagarofuranoids, diterpenoids, triterpenoids, tetraterpenes, phenylpropanoids, alkaloids, flavonoids, lignans, and others. The crude extracts and isolated constituents have exhibited a wide range of in vitro and in vivo pharmacological effects, including antitumor, cytotoxic, insecticidal, antimicrobial, anti-rheumatoid arthritis (RA), anti-inflammatory, anti-ageing and antioxidative, and neuroprotective activities. Plants of genus Celastrus have been confirmed to show a strong potential for therapeutic and health-maintaining effects, in light of their long traditional use and the phytochemical and pharmacological studies summarized here. Currently, pharmacological studies of this genus mainly focus on Celastrus paniculatus Willd. and Celastrus orbiculatus Thunb. Therefore, more pharmacological investigations should be implemented to support traditional uses of other medicinal plants of the genus Celastrus. Moreover, studies on the toxicity, bioavailability, and pharmacokinetics, in addition to clinical trials, are indispensable for assessing the safety and efficacy of the secondary metabolites or extracts obtained from plants belonging to this genus. Secondary metabolites studied in this article : (−)-epiafzelechin (Pubchem CID: 443639); celahypodiol (Pubchem CID: 11948700); celangulin I (Pubchem CID: 23252571); celangulin IV (Pubchem CID: 44149142); celangulin-V (Pubchem CID: 178554); celaspene A (Pubchem CID: 101880840); celaspene C (Pubchem CID: 101880842); celastrofuran A (Pubchem CID: 132487992); celastrofuran B (Pubchem CID: 132487993); celastrofuran C (Pubchem CID: 132487994); celastrofuran D (Pubchem CID: 132487995); celastrofuran E (Pubchem CID: 132487996); celastrofuran F (Pubchem CID: 132487997); celastrol (Pubchem CID: 122724); combretastatin D-2 (Pubchem CID: 11779322); erythrodiol (Pubchem CID: 101761); griffithane D (Pubchem CID: 56597215); hindsiilactone A (Pubchem CID: 102584176); hindsiiquinoflavan B (Pubchem CID: 102584175); isocorniculatolide A (Pubchem CID: 57331848); orthosphenic acid (Pubchem CID: 20056194); pristimerin (Pubchem CID: 159516); wilfornine G (Pubchem CID: 57395888); wilforol A (Pubchem CID: 10096097). Image 1 [ABSTRACT FROM AUTHOR]