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Aims: The study aimed to investigate the antihyperglycemic activity of Matricaria pubescens. Background: Matricaria pubescens (Def). Shultz (Asteraceae) is commonly used traditionally for the treatment of diabetes in Morocco. Objective: The present investigation aimed to assess the antihyperglycemic and antioxidant effects of the aqueous extract of the aerial part of Matricaria pubescens (M. pubescens). Methods: The effect of a single and repeated oral administration of the aqueous extract of aerial part of M. pubescens (AEAPMP) at a dose of 40 mg/kg on glucose was examined in normal and streptozotocin-induced diabetic rats. Additionally, histopathological examination of the pancreas and liver was carried out according to the Hematoxylin-Eosin method. The antioxidant activity was performed using the DPPH assay. Results: The results showed that the aqueous extract of M. pubescens (AEAPMP) exhibited a significant lowering activity on blood glucose levels in STZ-induced diabetic rats. In addition, AEAPMP ameliorated the histopathological tissues of the liver and pancreas. Furthermore, in vitro antioxidant activity of AEAPMP has been shown. Conclusion: In conclusion, this study demonstrates that M. pubescens possesses a beneficial effect against hyperglycemia associated with diabetes.