Background: Chronic insulin resistance (IR) is a basic part of the pathophysiology of gestational diabetes mellitus. Nutrition significantly impacts IR and weight loss reduces insulin levels, whereas weight gain increases the concentrations. Therefore, we surveyed the effect of nutrition intervention on IR in pregnant women and whether this effect is irrespective of weight gaining in accordance with Institute of Medicine limits. Methods: This prospective, randomized clinical trial was carried out among 150 primiparous pregnant mothers in fifteen health centers, five hospitals, and 15 private obstetrical offices in Isfahan. The nutrition intervention included education of healthy diet with emphasize on 50%–55% of total energy intake from carbohydrate (especially complex carbohydrates), 25%–30% from fat (to increase mono unsaturated fatty acids and decrease saturated and trans-fatty acids), and 15%–20% from protein during pregnancy for experimental group. The controls received the usual prenatal care by their health-care providers. Results: This trial decreased pregnancy-induced insulin increases (P = 0.01) and IR marginally (P = 0.05). ANCOVA demonstrated that control of gestational weight gaining was more effective to decrease IR (P = 0.02) while insulin values decreased by nutrition intervention and irrespective of weight control (P = 0.06). Fasting plasma glucose (FPG) concentrations did not decrease by intervention (P = 0.56) or weight management (P = 0.15). Conclusions: The current intervention was effective to decrease pregnancy-induced insulin increases and IR. Considering study results on FPG levels and incidence of GDM, we suggest repeat of study design in a larger sample.