Background and Aim: Dietary management and antidiabetic drugs are used as therapies for diabetic patients worldwide. Alginate nanofibers were developed as a digestible food product that provides sufficient calories. This study aimed to evaluate the effect of polyvinyl alcohol (PVA) and alginate nanofibers on weight gain, blood glucose levels, and insulin and other serum parameters in diabetic rats. Materials and Methods: A total of 24 male Wistar rats were divided into six groups: (C–) Control group, (C+) diabetic rats, (T1) diabetic rats + fasting treatment for 12 h, (T2) diabetic rats + nanofibers ad libitum, (T3) diabetic rats + metformin + nanofibers ad libitum, and (T4) diabetic rats + metformin. All groups were treated for 21 days. Weight gain was evaluated by comparing initial and final weights. Blood glucose levels were evaluated weekly. Serum parameters were also evaluated at the end of the study. All variables were analyzed statistically using analysis of variance followed by Tukey's post hoc test (p<0.05). Results: The T2, T3, and T4 groups showed a significant increase in weight compared to that of the C+ and T1 groups. The T3 group had the lowest blood glucose level of all groups at the end of the study. In the serum evaluation, the T2 and T3 groups showed a significant decrease compared to the C+ group for the following variables: Alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), creatinine, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β). In contrast, the T2 group showed a significant decrease compared to the T3 group for aspartate aminotransferase and insulin levels. Conclusion: PVA and alginate nanofibers can modulate obesity, reduce blood glucose levels, and reduce serum levels of insulin, ALT, ALP, GGT, creatinine, TNF-α, and IL-1β in diabetic rats.