INS and gestational diabetes: • GPR173 expression was identified in placental tissue.• GDM mice exhibited changes, including elevated blood glucose and lipid levels and reduced serum insulin, which these effects were reversed with PNX-20 treatment.• PNX-20 administration alleviated the excessive release of inflammatory factors and oxidative stress in GDM mice.• PNX-20 significantly suppressed the activated eIF-2α/ATF4 ER stress signaling pathway in GDM mice.