Phytochemical Profile, Antioxidant, Antidiabetic, and Antidiarrheal Potentials of <i>Hylocereus undatus</i> Leaf Extract: GC–MS and In Silico Insights

Hylocereus undatus (Haworth) Britton and Rose is a popular and extensively used medicinal herb, especially in Asia, which encompasses several medicinal phytochemicals that possess curative properties. This study explored its antioxidant, antidiabetic, and antidiarrheal properties by gas chromatography‐mass spectrometry (GC–MS)‐based identification of bioactive compounds along with an in silico study. Leaf extract of H. undatus was prepared using n ‐hexane. In vitro antioxidant activities were evaluated using spectrophotometric methods. In vivo antidiabetic activity was determined by oral glucose tolerance test, and antidiarrheal activity was assessed via castor oil–induced diarrhea in mice. The bioactive compounds were identified via GC–MS. An in silico study was done by a computer‐aided model using the α‐amylase protein. The phytochemical screening exhibited a wide variety of plant metabolites. The total phenolic, total flavonoid, total tannin, and total antioxidant capacity were estimated as 29.73 ± 0.33 mg of GAE/g, 69.3 ± 6.61 mg of QE/g, 14.35 ± 0.221 mg of GAE/g, and 115.58 ± 1.43 mg of AAE/g, respectively. The OGTT test of the extract at 500 mg/kg produced a noteworthy ( p &lt; 0.01) reduction in BGL at 30 min (14.6%), 60 min (26.4%), 90 min (40.9%), and 120 min (49.4%) post‐treatment compared to the control group. In the castor oil–induced diarrhea model, nHE (500 mg/kg, 39.58%) significantly ( p &lt; 0.01) delayed diarrhea onset and reduced total feces. The extent of these activities resembled that of standard loperamide (5 mg/kg, 58.33%). GC–MS identified 72 compounds, including β‐amyrone, lupeol, campesterol, stigmasterol, and vitamin E. In silico study also validated the potentialities of constituents of H. undatus . This is the first integrated study combining in vitro, in vivo, and in silico approaches to elucidate the pharmacological potential of H. undatus leaves, highlighting the extract as a promising source of therapeutic candidates. Further mechanistic studies are warranted.