Diabetes is a global health concern with significant implications for individuals and healthcare systems. Finding effective and safe antidiabetic agents is crucial for the management of this chronic disease. Natural products have emerged as potential alternatives to allopathic drugs, offering a vast source of bioactive compounds. In this study, we conducted an assessment of the antidiabetic potential of Origanum compactum essential oil, employing a two-pronged approach, i.e., experimental investigation and computational docking analysis. The results of gas chromatography–mass spectrometry (GC-MS) showed that thymol (54.6%), carvacrol (23.18%), and p-cymene (7.12%) were the major compounds. Experimental assessments revealed higher IC50 values (150 µg/mL for α-amylase; 120 µg/mL for α-glucosidase) of O. compactum oil, compared to the control drug acarbose. In silico analysis revealed the best binding affinity of the oil components (carvacrol and thymol) with human NADPH oxidase, while the lysosomal acid-α-glucosidase and salivary amylase also demonstrated good binding affinity towards carvacrol and thymol. Our findings highlight the translational potential of O. compactum oil-based treatment for diabetes mellitus and provide a basis for further studies on the modulation of NADPH oxidase, amylase inhibition, and α-glucosidase by antidiabetic natural products. However, further in vivo investigations are strongly required to confirm the results of in vitro antidiabetic effect of O. compactum EO.