Abstract Two major cannabinoids of cannabis, namely cannabidiol (CBD) and tetrahydrocannabinol (THC) have been reportedly used as alternative medicine for diabetes treatment in both pre-clinical and clinical research. However, their mechanisms of action still remain unclear. Therefore, this study aimed to evaluate the α-glucosidase inhibitory activity of THC, CBD and the standardized cannabinoid extracts. Based on in silico studies, THC generated hydrogen bonding and Van der Waals interactions, while CBD exhibited only Van der Waals interactions with functional residues of target α-glucosidase protein, with good binding energies of −7.5 and −6.9 kcal/mol, respectively. In addition, both of them showed excellent pharmacokinetic profiles with minor toxicity in terms of tumorigenic and reproductive effects. In addition, the enzyme based in...