Gestational diabetes mellitus (GDM) is one of the most prevalent metabolic diseases in pregnant women. In this study, we investigated the effects of Salusin-α in rodent models of GDM. We observed decreased levels of Salusin-α in the placental tissue of GDM mice. Salusin-α alleviated GDM symptoms by reducing blood glucose and increasing serum insulin levels. Further analysis revealed that Salusin-α improved lipid profiles and foetal outcomes in GDM mice. Additionally, Salusin-α mitigated oxidative and nitrosative stress in the placental tissue of GDM mice by enhancing the levels of Vitamin E, Vitamin C, and reduced GSH, while decreasing levels of TBARS and nitric oxide metabolites (nitrite + nitrate = NOx). Salusin-α also reduced the levels of MCP-1 and IL-8. Mechanically, Salusin-α inhibited the activation of p38/NF-κB by reducing phosphorylated p38 and phosphorylated NF-κB p65. In conclusion, our findings support the potential clinical application of Salusin-α as a novel peptide for molecular intervention in GDM.