Background: Diabetes mellitus (DM) is a heterogeneous metabolic disorder occurring due to absolute or relative deficiency of insulin and causing chronic hyperglycemia that leads to crippling complications associated with morbidity and mortality. Objectives: The objective of the present work is to investigate the comparative antihyperglycemic effects of Pleurotus ostreatus, Nigella sativa, and Zingiber officinale with metformin. Materials and Methods: The study was conducted from June 2017 to February 2018. In this study, rats were divided into six groups according to the treatment regimen. Each group comprised five rats. Serum analysis of glucose was conducted during the treatment. After animals were sacrificed, histopathological examination of the pancreas was carried out. Results: Histopathological examination showed that streptozotocin caused damage to pancreatic beta-cells which secrete the insulin. Treatment with metformin, N. sativa, mushroom, and ginger produced a significant improvement in the function of these cells, regeneration of cells, and decrease in serum glucose levels. Conclusion: In two groups, N. sativa and ginger, regeneration of beta islets was observed, along with a significant reduction in the serum glucose levels, which was found in other groups as well.