Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia resulting from impaired insulin secretion, insulin action, or both, and it is associated with severe microvascular and macrovascular complications. Despite the availability of several antidiabetic drugs, long-term therapy is often limited by adverse effects, reduced efficacy, high cost, and failure to prevent disease progression, highlighting the need for novel therapeutic strategies. Drug repurposing has emerged as an effective approach to identify new pharmacological uses for existing drugs with established safety profiles. Streptozotocin-induced diabetic rat models are widely used in experimental research due to their ability to mimic pancreatic β-cell destruction, oxidative stress, and metabolic abnormalities observed in human diabetes, making them suitable for preclinical evaluation of antidiabetic agents. Atovaquone, a hydroxynaphthoquinone derivative primarily used as an antiprotozoal and antimicrobial agent, has gained recent scientific interest for its potential metabolic and cytoprotective effects. Its ability to modulate mitochondrial electron transport, reduce oxidative stress, and influence cellular energy metabolism provides a strong rationale for exploring its antidiabetic potential. This review aims to critically evaluate the antidiabetic activity of Atovaquone in streptozotocin-induced diabetic rats by summarizing available preclinical evidence related to its effects on blood glucose levels, insulin sensitivity, lipid profile, oxidative stress markers, inflammatory mediators, and pancreatic histopathology. The findings from experimental studies suggest that Atovaquone may exert significant antihyperglycemic and antioxidant effects, contributing to improved metabolic control in diabetic conditions. However, further mechanistic investigations and well-designed clinical studies are necessary to validate these findings and establish its therapeutic relevance in diabetes management. This review highlights the potential of Atovaquone as a promising repurposed candidate for future antidiabetic drug development.