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Background: Diabetes mellitus (DM) has become a disease prevalent worldwide. Honey, which comprises predominantly bioactive constituents, has anti-inflammatory, antioxidant, and immunomodulating properties. Aim: Recent developments and benefits of natural products in treating various diseases have caught the attention of researchers. This study aims to investigate the antidiabetic effect of bee honey extract on induced diabetic Swiss mice. Materials and Methods: Fifty Swiss male mice were randomly assigned to five groups of 10 mice each. Group I served as the negative control; in group II, the mice received 2 mg/kg/b.wt of honey extract only; and groups III, IV, and V received cyclosporine (CsA) (20 mg/kg/day, s.c.) daily for 10 days prior to receiving streptozotocin (STZ) inoculated at multiple low doses (MLDSTZ) (30 mg/kg/day, i.p.) for five consecutive days. Group IV was administered with insulin initiated at a dose of 0.5 U/kg/b.wt as a standard treatment (positive control). Group V was administered 2 mg/kg/b.wt of honey extract, while group III received no treatment. Results: The results showed a significant hypoglycemic effect, increased body weight, increased liver glycogen levels, and the amelioration of antioxidant activities in groups IV and V compared with the diabetic group III. Moreover, serum matrix metalloproteinase (MMP-9) concentrations were significantly reduced in the mice treated with the insulin and honey extract in groups IV and V and the tissue inhibitor metalloproteinase-1 (TIMP-1) levels were significantly higher than the serum levels in group III. Furthermore, the histopathological examination of groups IV and V revealed regenerative changes with the restoration of normal islet cell architecture, as compared to the diabetic mice in group III. Compared to group I, group II showed no changes and exhibited non-significant data. Conclusion: Honey extract plays an effective role in improving all biomarkers in treated group V. Furthermore, MMP-9 and TIMP-1 are considered prognostic markers in the progression, severity, diagnosis, and treatment of type 1 DM. This may play an important role for the treatment of individuals in the future. [ABSTRACT FROM AUTHOR]